GI and Hepatology News

Effective ways to combat harmful viruses, bacteria, fungi, and parasitic worms have driven major advances in medicine and contributed to a significant increase in human life expectancy over the past century. However, as knowledge about the role of these microorganisms in promoting and maintaining health deepens, there is a need for a new look at the impact of these treatments.

The list of drugs that can directly alter the gut microbiota is long. In addition to antibiotics, antivirals, antifungals, anthelmintics, proton pump inhibitors, nonsteroidal anti-inflammatory drugs (NSAIDs), laxatives, oral antidiabetics, antidepressants, antipsychotics, statins, chemotherapeutics, and immunosuppressants can trigger dysbiosis.

A 2020 study published in Nature Communications, which analyzed the impact of common medications on the composition and metabolic function of the gut bacteria, showed that of the 41 classes of medications, researchers found that 19 were associated with changes in the microbiome, most notably antibiotics, proton pump inhibitors, laxatives, and metformin.

“There are still no protocols aimed at preserving the microbiota during pharmacological treatment. Future research should identify biomarkers of drug-induced dysbiosis and potentially adapt live biotherapeutics to counteract it,” said Maria Júlia Segantini, MD, a coloproctologist at the University of São Paulo, Brazil.

 

Known Facts

Antibiotics, antivirals, antifungals, and anthelmintics eliminate pathogens but can also disrupt the microbiota across the gut, skin, mouth, lungs, and genitourinary tract.

“This ecosystem is part of the innate immune system and helps to balance inflammation and homeostasis. Loss of microbial diversity alters interspecies interactions and changes nutrient availability, which can undermine the ability to fend off pathogens,” said Segantini, noting the role of microbiota in vitamin K and B-complex production.

“The microbiome may lose its ability to prevent pathogens from taking hold. This is due to the loss of microbial diversity, changes in interactions between species, and the availability of nutrients,” she added.

Antibiotics, as is well known, eliminate bacterial species indiscriminately, reduce the presence of beneficial bacteria in the gut, and, therefore, favor the growth of opportunistic pathogenic microorganisms. However, in addition to their direct effects on microorganisms, different medications can alter the intestinal microbiota through various mechanisms linked to their specific actions. Here are some examples:

Proton pump inhibitors: These can facilitate the translocation of bacteria from the mouth to the intestine and affect the metabolic functions of the intestinal microbiota. “In users of these medications, there may be an enrichment of pathways related to carbohydrate metabolism, such as glycolysis and pyruvate metabolism, indicating possible changes in intestinal metabolism,” Segantini explained.

NSAIDs: NSAIDs can modify the function and composition of the intestinal microbiota, favor the growth of pathogenic species, and reduce the diversity of preexisting bacteria by reducing the presence of beneficial commensal bacteria, such as Lactobacillus and Bifidobacterium. “This is due to changes in the permeability of the intestinal wall, due to the inhibition of prostaglandins that help maintain the integrity of the intestinal barrier, enteropathy induced by NSAIDs, and drug interactions,” said Segantini.

Laxatives: Accelerated intestinal transit using laxatives impairs the quality of the microbiota and alters bile acid. Osmotic agents, such as lactulose and polyethylene glycol, may decrease resistance to infection.

“Studies in animal models indicate that polyethylene glycol can increase the proportion of Bacteroides and reduce the abundance of Bacteroidales bacteria, with lasting repercussions on the intestinal microbiota. Stimulant laxatives, in addition to causing an acceleration of the evacuation flow, can lead to a decrease in the production of short-chain fatty acids, which are important for intestinal health,” Segantini explained.

Chemotherapeutics: Chemotherapeutic agents can significantly influence the intestinal microbiota and affect its composition, diversity, and functionality, which in turn can affect the efficacy of treatment and the occurrence of adverse effects. “5-fluorouracil led to a decrease in the abundance of beneficial anaerobic genera, such as Blautia, and an increase in opportunistic pathogens, such as Staphylococcus and Escherichia coli, during chemotherapy. In addition, it can lead to an increase in the abundance of Bacteroidetes and Proteobacteria while reducing Firmicutes and Actinobacteria. These changes can affect the function of the intestinal barrier and the immune response. Other problems related to chemotherapy-induced dysbiosis are the adverse effects themselves, such as diarrhea and mucositis,” said Segantini.

Statins: Animal studies suggest that treatment with statins, including atorvastatin, may alter the composition of the gut microbiota. “These changes include the reduction of beneficial bacteria, such as Akkermansia muciniphila, and the increase in intestinal pathogens, resulting in intestinal dysbiosis. The use of statins can affect the diversity of the intestinal microbiota, although the results vary according to the type of statin and the clinical context.”

“Statins can activate intestinal nuclear receptors, such as pregnane X receptors, which modulate the expression of genes involved in bile metabolism and the inflammatory response. This activation can contribute to changes in the intestinal microbiota and associated metabolic processes. Although statins play a fundamental role in reducing cardiovascular risk, their interactions with the intestinal microbiota can influence the efficacy of treatment and the profile of adverse effects,” said Segantini.

Immunosuppressants: The use of immunosuppressants, such as corticosteroids, tacrolimus, and mycophenolate, has been associated with changes in the composition of the intestinal microbiota. “Immunosuppressant-induced dysbiosis can compromise the intestinal barrier, increase permeability, and facilitate bacterial translocation. This can result in opportunistic infections by pathogens and post-transplant complications, such as graft rejection and post-transplant diabetes,” Segantini stated.

“Alteration of the gut microbiota by immunosuppressants may influence the host’s immune response. For example, tacrolimus has been associated with an increase in the abundance of Allobaculum, Bacteroides, and Lactobacillus, in addition to elevated levels of regulatory T cells in the colonic mucosa and circulation, suggesting a role in modulating gut immunity,” she said.

Antipsychotics: Antipsychotics can affect gut microbiota in several ways, influencing bacterial composition and diversity, which may contribute to adverse metabolic and gastrointestinal effects.

“Olanzapine, for example, has been shown in rodent studies to increase the abundance of Firmicutes and reduce that of Bacteroidetes, resulting in a higher Firmicutes/Bacteroidetes ratio, which is associated with weight gain and dyslipidemia,” said Segantini.

She stated that risperidone increased the abundance of Firmicutes and decreased that of Bacteroidetes in animal models, correlating with weight gain and reduced basal metabolic rate. “Fecal transfer from risperidone-treated mice to naive mice resulted in decreased metabolic rate, suggesting that the gut microbiota would mediate these effects.”

Treatment with aripiprazole increased microbial diversity and the abundance of Clostridium, Peptoclostridium, Intestinibacter, and Christensenellaceae, in addition to promoting increased intestinal permeability in animal models.

“Therefore, the use of these medications can lead to metabolic changes, such as weight gain, hyperglycemia, dyslipidemia, and hypertension. This is due to a decrease in the production of short-chain fatty acids, which are important for maintaining the integrity of the intestinal barrier. Another change frequently observed in clinical practice is constipation induced by these medications. This functional change can also generate changes in the intestinal microbiota,” she said.

Oral antidiabetic agents: Oral antidiabetic agents influence the intestinal microbiota in different ways, depending on the therapeutic class. However, not all drug interactions in the microbiome are harmful. Liraglutide, a GLP-1 receptor agonist, promotes the growth of beneficial bacteria associated with metabolism.

“Exenatide, another GLP-1 agonist, has varied effects and can increase both beneficial and inflammatory bacteria,” explained Álvaro Delgado, MD, a gastroenterologist at Hospital Alemão Oswaldo Cruz in São Paulo, Brazil.

“In humans, an increase in bacteria such as Faecalibacterium prausnitzii has been observed, with positive effects. However, more studies are needed to evaluate the clinical impacts,” he said, and that, in animal models, these changes caused by GLP-1 agonists are linked to metabolic changes, such as greater glucose tolerance.

Metformin has been linked to increased abundance of A muciniphila, a beneficial bacterium that degrades mucin and produces short-chain fatty acids. “These bacteria are associated with improved insulin sensitivity and reduced inflammation,” he said.

Segantini stated that studies in mice have shown that vildagliptin also plays a positive role in altering the composition of the intestinal microbiota, increasing the abundance of Lactobacillus and Roseburia, and reducing Oscillibacter. “This same beneficial effect is seen with the use of sitagliptin,” she said.

Studies in animal models have also indicated that empagliflozin and dapagliflozin increase the populations of short-chain fatty acid-producing bacteria, such as Bacteroides and Odoribacter, and reduce the populations of lipopolysaccharide-producing bacteria, such as Oscillibacter.

“There are still not many studies regarding the use of sulfonylureas on the intestinal microbiota, so their action on the microbiota is still controversial,” said Segantini.

Antivirals: Antiviral treatment can influence gut microbiota in complex ways, depending on the type of infection and medication used.

“Although many studies focus on the effects of viral infection on the microbiota, there is evidence that antiviral treatment can also restore the healthy composition of the microbiota, promoting additional benefits to gut and immune health,” said Segantini.

In mice with chronic hepatitis B, entecavir restored the alpha diversity of the gut microbiota, which was reduced due to infection. In addition, the recovery of beneficial bacteria, such as Akkermansia and Blautia, was observed, which was associated with the protection of the intestinal barrier and reduction of hepatic inflammation.

Studies have indicated that tenofovir may aid in the recovery of intestinal dysbiosis induced by chronic hepatitis B virus infection and promote the restoration of a healthy microbial composition.

“Specifically, an increase in Collinsella and Bifidobacterium, bacteria associated with the production of short-chain fatty acids and modulation of the immune response, was observed,” said Segantini.

The use of antiretrovirals, such as lopinavir and ritonavir, has been associated with changes in the composition of the intestinal microbiota in patients living with HIV.

“A decrease in Lachnospira, Butyricicoccus, Oscillospira, and Prevotella, bacteria that produce short-chain fatty acids that are important in intestinal health and in modulating the immune response, was observed.”

Antifungals: As a side effect, antifungals also eliminate commensal fungi, which “share intestinal niches with microbiota bacteria, balancing their immunological functions. When modified, they culminate in dysbiosis, worsening of inflammatory pathologies — such as colitis and allergic diseases — and can increase bacterial translocation,” said Segantini. 

For example, fluconazole reduces the abundance of Candida spp. while promoting the growth of fungi such as Aspergillus, Wallemia, and Epicoccum.

“A relative increase in Firmicutes and Proteobacteria and a decrease in Bacteroidetes, Deferribacteres, Patescibacteria, and Tenericutes were also observed,” she explained.

Anthelmintics: These also affect the intestinal bacterial and fungal microbiota and alter the modulation of the immune response, in addition to having specific effects depending on the type of drug used.

 

Clinical Advice

Symptoms of dysbiosis include abdominal distension, flatulence, constipation or diarrhea, pain, fatigue, and mood swings. “The diagnosis is made based on the clinical picture, since tests such as small intestinal bacterial overgrowth, which indicate metabolites of bacteria associated with dysbiosis, specific stool tests, and microbiota mapping with GI-MAP [Gastrointestinal Microbial Assay Plus], for example, are expensive, difficult to access, and often inconclusive for diagnosis and for assessing the cause of the microbiota alteration,” explained Fernando Seefelder Flaquer, MD, a gastroenterologist at Albert Einstein Israelite Hospital in São Paulo.

When caused by medication, dysbiosis tends to be reversed naturally after discontinuation of the drug. “However, in medications with a high chance of altering the microbiota, probiotics can be used as prevention,” said Flaquer.

“To avoid problems, it is important to use antibiotics with caution and prefer, when possible, those with a reduced spectrum,” advised Delgado.

“Supplementation with probiotics and prebiotics can help maintain the balance of the microbiota, but it should be evaluated on a case-by-case basis, as its indications are still restricted at present.”

Currently, dysbiosis management relies on nutritional support and lifestyle modifications. “Physical exercise, management of psychological changes, and use of probiotics and prebiotics. In specific cases, individualized treatment may even require the administration of some types of antibiotics,” explained Segantini.

Although fecal microbiota transplantation (FMT) has been widely discussed and increasingly studied, it should still be approached with caution. While promising, FMT remains experimental for most conditions, and its use outside research settings should be carefully considered, particularly in patients who are immunocompromised or have compromised intestinal barriers.

“Currently, the treatment has stood out as promising for cases of recurrent Clostridioides difficile infection, being the only consolidated clinical indication,” said Segantini.

 

Science Hype

The interest in gut microbiome research has undoubtedly driven important scientific advances, but it also risks exaggeration. While the field holds enormous promise, much of the research remains in its early stages.

“The indiscriminate use of probiotics and reliance on microbiota analysis tests for personalized probiotic prescriptions are growing concerns,” Delgado warned. “We need to bridge the gap between basic science and clinical application. When that translation happens, it could revolutionize care for many diseases.”

Flaquer emphasized a broader issue: “There has been an overvaluation of dysbiosis and microbiota-focused treatments as cure-alls for a wide range of conditions — often subjective or lacking solid scientific correlation — such as depression, anxiety, fatigue, cancer, and even autism.”

With ongoing advances in microbiome research, understanding the impact of this complex ecosystem on human health has become essential across all medical specialties. In pediatrics, for instance, microbiota plays a critical role in immune and metabolic development, particularly in preventing conditions such as allergies and obesity.

In digestive surgery, preoperative use of probiotics has been shown to reduce complications and enhance postoperative recovery. Neurological research has highlighted the gut-brain axis as a potential factor in the development of neurodegenerative diseases. In gynecology, regulating the vaginal microbiota is key to preventing infections and complications during pregnancy.

“Given the connections between the microbiota and both intestinal and systemic diseases, every medical specialist should understand how it relates to the conditions they treat daily,” concluded Flaquer.

This story was translated from Medscape’s Portuguese edition.

Effective ways to combat harmful viruses, bacteria, fungi, and parasitic worms have driven major advances in medicine and contributed to a significant increase in human life expectancy over the past century. However, as knowledge about the role of these microorganisms in promoting and maintaining health deepens, there is a need for a new look at the impact of these treatments.

The list of drugs that can directly alter the gut microbiota is long. In addition to antibiotics, antivirals, antifungals, anthelmintics, proton pump inhibitors, nonsteroidal anti-inflammatory drugs (NSAIDs), laxatives, oral antidiabetics, antidepressants, antipsychotics, statins, chemotherapeutics, and immunosuppressants can trigger dysbiosis.

A 2020 study published in Nature Communications, which analyzed the impact of common medications on the composition and metabolic function of the gut bacteria, showed that of the 41 classes of medications, researchers found that 19 were associated with changes in the microbiome, most notably antibiotics, proton pump inhibitors, laxatives, and metformin.

“There are still no protocols aimed at preserving the microbiota during pharmacological treatment. Future research should identify biomarkers of drug-induced dysbiosis and potentially adapt live biotherapeutics to counteract it,” said Maria Júlia Segantini, MD, a coloproctologist at the University of São Paulo, Brazil.

 

Known Facts

Antibiotics, antivirals, antifungals, and anthelmintics eliminate pathogens but can also disrupt the microbiota across the gut, skin, mouth, lungs, and genitourinary tract.

“This ecosystem is part of the innate immune system and helps to balance inflammation and homeostasis. Loss of microbial diversity alters interspecies interactions and changes nutrient availability, which can undermine the ability to fend off pathogens,” said Segantini, noting the role of microbiota in vitamin K and B-complex production.

“The microbiome may lose its ability to prevent pathogens from taking hold. This is due to the loss of microbial diversity, changes in interactions between species, and the availability of nutrients,” she added.

Antibiotics, as is well known, eliminate bacterial species indiscriminately, reduce the presence of beneficial bacteria in the gut, and, therefore, favor the growth of opportunistic pathogenic microorganisms. However, in addition to their direct effects on microorganisms, different medications can alter the intestinal microbiota through various mechanisms linked to their specific actions. Here are some examples:

Proton pump inhibitors: These can facilitate the translocation of bacteria from the mouth to the intestine and affect the metabolic functions of the intestinal microbiota. “In users of these medications, there may be an enrichment of pathways related to carbohydrate metabolism, such as glycolysis and pyruvate metabolism, indicating possible changes in intestinal metabolism,” Segantini explained.

NSAIDs: NSAIDs can modify the function and composition of the intestinal microbiota, favor the growth of pathogenic species, and reduce the diversity of preexisting bacteria by reducing the presence of beneficial commensal bacteria, such as Lactobacillus and Bifidobacterium. “This is due to changes in the permeability of the intestinal wall, due to the inhibition of prostaglandins that help maintain the integrity of the intestinal barrier, enteropathy induced by NSAIDs, and drug interactions,” said Segantini.

Laxatives: Accelerated intestinal transit using laxatives impairs the quality of the microbiota and alters bile acid. Osmotic agents, such as lactulose and polyethylene glycol, may decrease resistance to infection.

“Studies in animal models indicate that polyethylene glycol can increase the proportion of Bacteroides and reduce the abundance of Bacteroidales bacteria, with lasting repercussions on the intestinal microbiota. Stimulant laxatives, in addition to causing an acceleration of the evacuation flow, can lead to a decrease in the production of short-chain fatty acids, which are important for intestinal health,” Segantini explained.

Chemotherapeutics: Chemotherapeutic agents can significantly influence the intestinal microbiota and affect its composition, diversity, and functionality, which in turn can affect the efficacy of treatment and the occurrence of adverse effects. “5-fluorouracil led to a decrease in the abundance of beneficial anaerobic genera, such as Blautia, and an increase in opportunistic pathogens, such as Staphylococcus and Escherichia coli, during chemotherapy. In addition, it can lead to an increase in the abundance of Bacteroidetes and Proteobacteria while reducing Firmicutes and Actinobacteria. These changes can affect the function of the intestinal barrier and the immune response. Other problems related to chemotherapy-induced dysbiosis are the adverse effects themselves, such as diarrhea and mucositis,” said Segantini.

Statins: Animal studies suggest that treatment with statins, including atorvastatin, may alter the composition of the gut microbiota. “These changes include the reduction of beneficial bacteria, such as Akkermansia muciniphila, and the increase in intestinal pathogens, resulting in intestinal dysbiosis. The use of statins can affect the diversity of the intestinal microbiota, although the results vary according to the type of statin and the clinical context.”

“Statins can activate intestinal nuclear receptors, such as pregnane X receptors, which modulate the expression of genes involved in bile metabolism and the inflammatory response. This activation can contribute to changes in the intestinal microbiota and associated metabolic processes. Although statins play a fundamental role in reducing cardiovascular risk, their interactions with the intestinal microbiota can influence the efficacy of treatment and the profile of adverse effects,” said Segantini.

Immunosuppressants: The use of immunosuppressants, such as corticosteroids, tacrolimus, and mycophenolate, has been associated with changes in the composition of the intestinal microbiota. “Immunosuppressant-induced dysbiosis can compromise the intestinal barrier, increase permeability, and facilitate bacterial translocation. This can result in opportunistic infections by pathogens and post-transplant complications, such as graft rejection and post-transplant diabetes,” Segantini stated.

“Alteration of the gut microbiota by immunosuppressants may influence the host’s immune response. For example, tacrolimus has been associated with an increase in the abundance of Allobaculum, Bacteroides, and Lactobacillus, in addition to elevated levels of regulatory T cells in the colonic mucosa and circulation, suggesting a role in modulating gut immunity,” she said.

Antipsychotics: Antipsychotics can affect gut microbiota in several ways, influencing bacterial composition and diversity, which may contribute to adverse metabolic and gastrointestinal effects.

“Olanzapine, for example, has been shown in rodent studies to increase the abundance of Firmicutes and reduce that of Bacteroidetes, resulting in a higher Firmicutes/Bacteroidetes ratio, which is associated with weight gain and dyslipidemia,” said Segantini.

She stated that risperidone increased the abundance of Firmicutes and decreased that of Bacteroidetes in animal models, correlating with weight gain and reduced basal metabolic rate. “Fecal transfer from risperidone-treated mice to naive mice resulted in decreased metabolic rate, suggesting that the gut microbiota would mediate these effects.”

Treatment with aripiprazole increased microbial diversity and the abundance of Clostridium, Peptoclostridium, Intestinibacter, and Christensenellaceae, in addition to promoting increased intestinal permeability in animal models.

“Therefore, the use of these medications can lead to metabolic changes, such as weight gain, hyperglycemia, dyslipidemia, and hypertension. This is due to a decrease in the production of short-chain fatty acids, which are important for maintaining the integrity of the intestinal barrier. Another change frequently observed in clinical practice is constipation induced by these medications. This functional change can also generate changes in the intestinal microbiota,” she said.

Oral antidiabetic agents: Oral antidiabetic agents influence the intestinal microbiota in different ways, depending on the therapeutic class. However, not all drug interactions in the microbiome are harmful. Liraglutide, a GLP-1 receptor agonist, promotes the growth of beneficial bacteria associated with metabolism.

“Exenatide, another GLP-1 agonist, has varied effects and can increase both beneficial and inflammatory bacteria,” explained Álvaro Delgado, MD, a gastroenterologist at Hospital Alemão Oswaldo Cruz in São Paulo, Brazil.

“In humans, an increase in bacteria such as Faecalibacterium prausnitzii has been observed, with positive effects. However, more studies are needed to evaluate the clinical impacts,” he said, and that, in animal models, these changes caused by GLP-1 agonists are linked to metabolic changes, such as greater glucose tolerance.

Metformin has been linked to increased abundance of A muciniphila, a beneficial bacterium that degrades mucin and produces short-chain fatty acids. “These bacteria are associated with improved insulin sensitivity and reduced inflammation,” he said.

Segantini stated that studies in mice have shown that vildagliptin also plays a positive role in altering the composition of the intestinal microbiota, increasing the abundance of Lactobacillus and Roseburia, and reducing Oscillibacter. “This same beneficial effect is seen with the use of sitagliptin,” she said.

Studies in animal models have also indicated that empagliflozin and dapagliflozin increase the populations of short-chain fatty acid-producing bacteria, such as Bacteroides and Odoribacter, and reduce the populations of lipopolysaccharide-producing bacteria, such as Oscillibacter.

“There are still not many studies regarding the use of sulfonylureas on the intestinal microbiota, so their action on the microbiota is still controversial,” said Segantini.

Antivirals: Antiviral treatment can influence gut microbiota in complex ways, depending on the type of infection and medication used.

“Although many studies focus on the effects of viral infection on the microbiota, there is evidence that antiviral treatment can also restore the healthy composition of the microbiota, promoting additional benefits to gut and immune health,” said Segantini.

In mice with chronic hepatitis B, entecavir restored the alpha diversity of the gut microbiota, which was reduced due to infection. In addition, the recovery of beneficial bacteria, such as Akkermansia and Blautia, was observed, which was associated with the protection of the intestinal barrier and reduction of hepatic inflammation.

Studies have indicated that tenofovir may aid in the recovery of intestinal dysbiosis induced by chronic hepatitis B virus infection and promote the restoration of a healthy microbial composition.

“Specifically, an increase in Collinsella and Bifidobacterium, bacteria associated with the production of short-chain fatty acids and modulation of the immune response, was observed,” said Segantini.

The use of antiretrovirals, such as lopinavir and ritonavir, has been associated with changes in the composition of the intestinal microbiota in patients living with HIV.

“A decrease in Lachnospira, Butyricicoccus, Oscillospira, and Prevotella, bacteria that produce short-chain fatty acids that are important in intestinal health and in modulating the immune response, was observed.”

Antifungals: As a side effect, antifungals also eliminate commensal fungi, which “share intestinal niches with microbiota bacteria, balancing their immunological functions. When modified, they culminate in dysbiosis, worsening of inflammatory pathologies — such as colitis and allergic diseases — and can increase bacterial translocation,” said Segantini. 

For example, fluconazole reduces the abundance of Candida spp. while promoting the growth of fungi such as Aspergillus, Wallemia, and Epicoccum.

“A relative increase in Firmicutes and Proteobacteria and a decrease in Bacteroidetes, Deferribacteres, Patescibacteria, and Tenericutes were also observed,” she explained.

Anthelmintics: These also affect the intestinal bacterial and fungal microbiota and alter the modulation of the immune response, in addition to having specific effects depending on the type of drug used.

 

Clinical Advice

Symptoms of dysbiosis include abdominal distension, flatulence, constipation or diarrhea, pain, fatigue, and mood swings. “The diagnosis is made based on the clinical picture, since tests such as small intestinal bacterial overgrowth, which indicate metabolites of bacteria associated with dysbiosis, specific stool tests, and microbiota mapping with GI-MAP [Gastrointestinal Microbial Assay Plus], for example, are expensive, difficult to access, and often inconclusive for diagnosis and for assessing the cause of the microbiota alteration,” explained Fernando Seefelder Flaquer, MD, a gastroenterologist at Albert Einstein Israelite Hospital in São Paulo.

When caused by medication, dysbiosis tends to be reversed naturally after discontinuation of the drug. “However, in medications with a high chance of altering the microbiota, probiotics can be used as prevention,” said Flaquer.

“To avoid problems, it is important to use antibiotics with caution and prefer, when possible, those with a reduced spectrum,” advised Delgado.

“Supplementation with probiotics and prebiotics can help maintain the balance of the microbiota, but it should be evaluated on a case-by-case basis, as its indications are still restricted at present.”

Currently, dysbiosis management relies on nutritional support and lifestyle modifications. “Physical exercise, management of psychological changes, and use of probiotics and prebiotics. In specific cases, individualized treatment may even require the administration of some types of antibiotics,” explained Segantini.

Although fecal microbiota transplantation (FMT) has been widely discussed and increasingly studied, it should still be approached with caution. While promising, FMT remains experimental for most conditions, and its use outside research settings should be carefully considered, particularly in patients who are immunocompromised or have compromised intestinal barriers.

“Currently, the treatment has stood out as promising for cases of recurrent Clostridioides difficile infection, being the only consolidated clinical indication,” said Segantini.

 

Science Hype

The interest in gut microbiome research has undoubtedly driven important scientific advances, but it also risks exaggeration. While the field holds enormous promise, much of the research remains in its early stages.

“The indiscriminate use of probiotics and reliance on microbiota analysis tests for personalized probiotic prescriptions are growing concerns,” Delgado warned. “We need to bridge the gap between basic science and clinical application. When that translation happens, it could revolutionize care for many diseases.”

Flaquer emphasized a broader issue: “There has been an overvaluation of dysbiosis and microbiota-focused treatments as cure-alls for a wide range of conditions — often subjective or lacking solid scientific correlation — such as depression, anxiety, fatigue, cancer, and even autism.”

With ongoing advances in microbiome research, understanding the impact of this complex ecosystem on human health has become essential across all medical specialties. In pediatrics, for instance, microbiota plays a critical role in immune and metabolic development, particularly in preventing conditions such as allergies and obesity.

In digestive surgery, preoperative use of probiotics has been shown to reduce complications and enhance postoperative recovery. Neurological research has highlighted the gut-brain axis as a potential factor in the development of neurodegenerative diseases. In gynecology, regulating the vaginal microbiota is key to preventing infections and complications during pregnancy.

“Given the connections between the microbiota and both intestinal and systemic diseases, every medical specialist should understand how it relates to the conditions they treat daily,” concluded Flaquer.

This story was translated from Medscape’s Portuguese edition.

Effective ways to combat harmful viruses, bacteria, fungi, and parasitic worms have driven major advances in medicine and contributed to a significant increase in human life expectancy over the past century. However, as knowledge about the role of these microorganisms in promoting and maintaining health deepens, there is a need for a new look at the impact of these treatments.

The list of drugs that can directly alter the gut microbiota is long. In addition to antibiotics, antivirals, antifungals, anthelmintics, proton pump inhibitors, nonsteroidal anti-inflammatory drugs (NSAIDs), laxatives, oral antidiabetics, antidepressants, antipsychotics, statins, chemotherapeutics, and immunosuppressants can trigger dysbiosis.

A 2020 study published in Nature Communications, which analyzed the impact of common medications on the composition and metabolic function of the gut bacteria, showed that of the 41 classes of medications, researchers found that 19 were associated with changes in the microbiome, most notably antibiotics, proton pump inhibitors, laxatives, and metformin.

“There are still no protocols aimed at preserving the microbiota during pharmacological treatment. Future research should identify biomarkers of drug-induced dysbiosis and potentially adapt live biotherapeutics to counteract it,” said Maria Júlia Segantini, MD, a coloproctologist at the University of São Paulo, Brazil.

 

Known Facts

Antibiotics, antivirals, antifungals, and anthelmintics eliminate pathogens but can also disrupt the microbiota across the gut, skin, mouth, lungs, and genitourinary tract.

“This ecosystem is part of the innate immune system and helps to balance inflammation and homeostasis. Loss of microbial diversity alters interspecies interactions and changes nutrient availability, which can undermine the ability to fend off pathogens,” said Segantini, noting the role of microbiota in vitamin K and B-complex production.

“The microbiome may lose its ability to prevent pathogens from taking hold. This is due to the loss of microbial diversity, changes in interactions between species, and the availability of nutrients,” she added.

Antibiotics, as is well known, eliminate bacterial species indiscriminately, reduce the presence of beneficial bacteria in the gut, and, therefore, favor the growth of opportunistic pathogenic microorganisms. However, in addition to their direct effects on microorganisms, different medications can alter the intestinal microbiota through various mechanisms linked to their specific actions. Here are some examples:

Proton pump inhibitors: These can facilitate the translocation of bacteria from the mouth to the intestine and affect the metabolic functions of the intestinal microbiota. “In users of these medications, there may be an enrichment of pathways related to carbohydrate metabolism, such as glycolysis and pyruvate metabolism, indicating possible changes in intestinal metabolism,” Segantini explained.

NSAIDs: NSAIDs can modify the function and composition of the intestinal microbiota, favor the growth of pathogenic species, and reduce the diversity of preexisting bacteria by reducing the presence of beneficial commensal bacteria, such as Lactobacillus and Bifidobacterium. “This is due to changes in the permeability of the intestinal wall, due to the inhibition of prostaglandins that help maintain the integrity of the intestinal barrier, enteropathy induced by NSAIDs, and drug interactions,” said Segantini.

Laxatives: Accelerated intestinal transit using laxatives impairs the quality of the microbiota and alters bile acid. Osmotic agents, such as lactulose and polyethylene glycol, may decrease resistance to infection.

“Studies in animal models indicate that polyethylene glycol can increase the proportion of Bacteroides and reduce the abundance of Bacteroidales bacteria, with lasting repercussions on the intestinal microbiota. Stimulant laxatives, in addition to causing an acceleration of the evacuation flow, can lead to a decrease in the production of short-chain fatty acids, which are important for intestinal health,” Segantini explained.

Chemotherapeutics: Chemotherapeutic agents can significantly influence the intestinal microbiota and affect its composition, diversity, and functionality, which in turn can affect the efficacy of treatment and the occurrence of adverse effects. “5-fluorouracil led to a decrease in the abundance of beneficial anaerobic genera, such as Blautia, and an increase in opportunistic pathogens, such as Staphylococcus and Escherichia coli, during chemotherapy. In addition, it can lead to an increase in the abundance of Bacteroidetes and Proteobacteria while reducing Firmicutes and Actinobacteria. These changes can affect the function of the intestinal barrier and the immune response. Other problems related to chemotherapy-induced dysbiosis are the adverse effects themselves, such as diarrhea and mucositis,” said Segantini.

Statins: Animal studies suggest that treatment with statins, including atorvastatin, may alter the composition of the gut microbiota. “These changes include the reduction of beneficial bacteria, such as Akkermansia muciniphila, and the increase in intestinal pathogens, resulting in intestinal dysbiosis. The use of statins can affect the diversity of the intestinal microbiota, although the results vary according to the type of statin and the clinical context.”

“Statins can activate intestinal nuclear receptors, such as pregnane X receptors, which modulate the expression of genes involved in bile metabolism and the inflammatory response. This activation can contribute to changes in the intestinal microbiota and associated metabolic processes. Although statins play a fundamental role in reducing cardiovascular risk, their interactions with the intestinal microbiota can influence the efficacy of treatment and the profile of adverse effects,” said Segantini.

Immunosuppressants: The use of immunosuppressants, such as corticosteroids, tacrolimus, and mycophenolate, has been associated with changes in the composition of the intestinal microbiota. “Immunosuppressant-induced dysbiosis can compromise the intestinal barrier, increase permeability, and facilitate bacterial translocation. This can result in opportunistic infections by pathogens and post-transplant complications, such as graft rejection and post-transplant diabetes,” Segantini stated.

“Alteration of the gut microbiota by immunosuppressants may influence the host’s immune response. For example, tacrolimus has been associated with an increase in the abundance of Allobaculum, Bacteroides, and Lactobacillus, in addition to elevated levels of regulatory T cells in the colonic mucosa and circulation, suggesting a role in modulating gut immunity,” she said.

Antipsychotics: Antipsychotics can affect gut microbiota in several ways, influencing bacterial composition and diversity, which may contribute to adverse metabolic and gastrointestinal effects.

“Olanzapine, for example, has been shown in rodent studies to increase the abundance of Firmicutes and reduce that of Bacteroidetes, resulting in a higher Firmicutes/Bacteroidetes ratio, which is associated with weight gain and dyslipidemia,” said Segantini.

She stated that risperidone increased the abundance of Firmicutes and decreased that of Bacteroidetes in animal models, correlating with weight gain and reduced basal metabolic rate. “Fecal transfer from risperidone-treated mice to naive mice resulted in decreased metabolic rate, suggesting that the gut microbiota would mediate these effects.”

Treatment with aripiprazole increased microbial diversity and the abundance of Clostridium, Peptoclostridium, Intestinibacter, and Christensenellaceae, in addition to promoting increased intestinal permeability in animal models.

“Therefore, the use of these medications can lead to metabolic changes, such as weight gain, hyperglycemia, dyslipidemia, and hypertension. This is due to a decrease in the production of short-chain fatty acids, which are important for maintaining the integrity of the intestinal barrier. Another change frequently observed in clinical practice is constipation induced by these medications. This functional change can also generate changes in the intestinal microbiota,” she said.

Oral antidiabetic agents: Oral antidiabetic agents influence the intestinal microbiota in different ways, depending on the therapeutic class. However, not all drug interactions in the microbiome are harmful. Liraglutide, a GLP-1 receptor agonist, promotes the growth of beneficial bacteria associated with metabolism.

“Exenatide, another GLP-1 agonist, has varied effects and can increase both beneficial and inflammatory bacteria,” explained Álvaro Delgado, MD, a gastroenterologist at Hospital Alemão Oswaldo Cruz in São Paulo, Brazil.

“In humans, an increase in bacteria such as Faecalibacterium prausnitzii has been observed, with positive effects. However, more studies are needed to evaluate the clinical impacts,” he said, and that, in animal models, these changes caused by GLP-1 agonists are linked to metabolic changes, such as greater glucose tolerance.

Metformin has been linked to increased abundance of A muciniphila, a beneficial bacterium that degrades mucin and produces short-chain fatty acids. “These bacteria are associated with improved insulin sensitivity and reduced inflammation,” he said.

Segantini stated that studies in mice have shown that vildagliptin also plays a positive role in altering the composition of the intestinal microbiota, increasing the abundance of Lactobacillus and Roseburia, and reducing Oscillibacter. “This same beneficial effect is seen with the use of sitagliptin,” she said.

Studies in animal models have also indicated that empagliflozin and dapagliflozin increase the populations of short-chain fatty acid-producing bacteria, such as Bacteroides and Odoribacter, and reduce the populations of lipopolysaccharide-producing bacteria, such as Oscillibacter.

“There are still not many studies regarding the use of sulfonylureas on the intestinal microbiota, so their action on the microbiota is still controversial,” said Segantini.

Antivirals: Antiviral treatment can influence gut microbiota in complex ways, depending on the type of infection and medication used.

“Although many studies focus on the effects of viral infection on the microbiota, there is evidence that antiviral treatment can also restore the healthy composition of the microbiota, promoting additional benefits to gut and immune health,” said Segantini.

In mice with chronic hepatitis B, entecavir restored the alpha diversity of the gut microbiota, which was reduced due to infection. In addition, the recovery of beneficial bacteria, such as Akkermansia and Blautia, was observed, which was associated with the protection of the intestinal barrier and reduction of hepatic inflammation.

Studies have indicated that tenofovir may aid in the recovery of intestinal dysbiosis induced by chronic hepatitis B virus infection and promote the restoration of a healthy microbial composition.

“Specifically, an increase in Collinsella and Bifidobacterium, bacteria associated with the production of short-chain fatty acids and modulation of the immune response, was observed,” said Segantini.

The use of antiretrovirals, such as lopinavir and ritonavir, has been associated with changes in the composition of the intestinal microbiota in patients living with HIV.

“A decrease in Lachnospira, Butyricicoccus, Oscillospira, and Prevotella, bacteria that produce short-chain fatty acids that are important in intestinal health and in modulating the immune response, was observed.”

Antifungals: As a side effect, antifungals also eliminate commensal fungi, which “share intestinal niches with microbiota bacteria, balancing their immunological functions. When modified, they culminate in dysbiosis, worsening of inflammatory pathologies — such as colitis and allergic diseases — and can increase bacterial translocation,” said Segantini. 

For example, fluconazole reduces the abundance of Candida spp. while promoting the growth of fungi such as Aspergillus, Wallemia, and Epicoccum.

“A relative increase in Firmicutes and Proteobacteria and a decrease in Bacteroidetes, Deferribacteres, Patescibacteria, and Tenericutes were also observed,” she explained.

Anthelmintics: These also affect the intestinal bacterial and fungal microbiota and alter the modulation of the immune response, in addition to having specific effects depending on the type of drug used.

 

Clinical Advice

Symptoms of dysbiosis include abdominal distension, flatulence, constipation or diarrhea, pain, fatigue, and mood swings. “The diagnosis is made based on the clinical picture, since tests such as small intestinal bacterial overgrowth, which indicate metabolites of bacteria associated with dysbiosis, specific stool tests, and microbiota mapping with GI-MAP [Gastrointestinal Microbial Assay Plus], for example, are expensive, difficult to access, and often inconclusive for diagnosis and for assessing the cause of the microbiota alteration,” explained Fernando Seefelder Flaquer, MD, a gastroenterologist at Albert Einstein Israelite Hospital in São Paulo.

When caused by medication, dysbiosis tends to be reversed naturally after discontinuation of the drug. “However, in medications with a high chance of altering the microbiota, probiotics can be used as prevention,” said Flaquer.

“To avoid problems, it is important to use antibiotics with caution and prefer, when possible, those with a reduced spectrum,” advised Delgado.

“Supplementation with probiotics and prebiotics can help maintain the balance of the microbiota, but it should be evaluated on a case-by-case basis, as its indications are still restricted at present.”

Currently, dysbiosis management relies on nutritional support and lifestyle modifications. “Physical exercise, management of psychological changes, and use of probiotics and prebiotics. In specific cases, individualized treatment may even require the administration of some types of antibiotics,” explained Segantini.

Although fecal microbiota transplantation (FMT) has been widely discussed and increasingly studied, it should still be approached with caution. While promising, FMT remains experimental for most conditions, and its use outside research settings should be carefully considered, particularly in patients who are immunocompromised or have compromised intestinal barriers.

“Currently, the treatment has stood out as promising for cases of recurrent Clostridioides difficile infection, being the only consolidated clinical indication,” said Segantini.

 

Science Hype

The interest in gut microbiome research has undoubtedly driven important scientific advances, but it also risks exaggeration. While the field holds enormous promise, much of the research remains in its early stages.

“The indiscriminate use of probiotics and reliance on microbiota analysis tests for personalized probiotic prescriptions are growing concerns,” Delgado warned. “We need to bridge the gap between basic science and clinical application. When that translation happens, it could revolutionize care for many diseases.”

Flaquer emphasized a broader issue: “There has been an overvaluation of dysbiosis and microbiota-focused treatments as cure-alls for a wide range of conditions — often subjective or lacking solid scientific correlation — such as depression, anxiety, fatigue, cancer, and even autism.”

With ongoing advances in microbiome research, understanding the impact of this complex ecosystem on human health has become essential across all medical specialties. In pediatrics, for instance, microbiota plays a critical role in immune and metabolic development, particularly in preventing conditions such as allergies and obesity.

In digestive surgery, preoperative use of probiotics has been shown to reduce complications and enhance postoperative recovery. Neurological research has highlighted the gut-brain axis as a potential factor in the development of neurodegenerative diseases. In gynecology, regulating the vaginal microbiota is key to preventing infections and complications during pregnancy.

“Given the connections between the microbiota and both intestinal and systemic diseases, every medical specialist should understand how it relates to the conditions they treat daily,” concluded Flaquer.

This story was translated from Medscape’s Portuguese edition.

Antibiotic treatment while awaiting appendectomy does not lower risk for appendiceal perforation in patients with uncomplicated acute appendicitis, according to a new study.

While the percentage of surgical site infections (SSIs) was small for both groups, patients who received antibiotics during the waiting period had lower rates of these infections.

The trial — titled PERFECT-Antibiotics — was a substudy embedded in a larger PERFECT clinical trial, which aimed to determine whether an in-hospital delay of appendectomy resulted in increased risk for appendiceal perforation when compared to emergent surgery.

The trial “concluded that appendectomy does not need to be performed promptly in acute uncomplicated appendicitis and can be scheduled within 24 hours without increasing complications,” senior author Panu Mentula, MD, of the Department of Gastroenterological Surgery, Helsinki University Hospital, Helsinki, Finland, and colleagues wrote in the study. “The next question is whether preoperatively started antibiotic treatment reduces the risk of appendiceal perforations.”

The findings were published online in JAMA Surgery on May 14, 2025.

 

Trial Design

PERFECT-Antibiotics was an open-label, randomized trial conducted at two hospitals in Finland and one hospital in Norway. Researchers enrolled 1774 individuals diagnosed with acute uncomplicated appendicitis, diagnosed clinically or via imaging. Patients were placed in one of two groups: The antibiotic group received intravenous (IV) cefuroxime (1500 mg) and metronidazole (500 mg) every 8 hours until surgery, while the nonantibiotic group waited for surgery without antibiotics.

All patients received one dose of IV cefuroxime (1500 mg) and metronidazole (500 mg) during anesthesia induction. The primary outcome was perforated appendicitis and secondary outcomes included complication rate and SSIs within 30 days of follow-up.

The median age of patients was 35 years (interquartile range [IQR], 28-46 years), and 55% of patients were men. Patients waited a median time of 9 hours (IQR, 4.3-15.5) from study randomization to undergoing surgery.

 

No Difference in Appendiceal Perforation

Of the 888 patients in the preoperative antibiotic group, 26.2% received one dose, 38.7% received two doses, 22.6% received three doses, and 11.8% received four or more doses of antibiotics, including the antibiotic dose given during anesthesia. A total of 74 patients (8.3%) in this group had a perforated appendix.

Of the 886 patients not given preoperative antibiotics, 79 (8.9%) had a perforated appendix, which met the predetermined noninferiority threshold.

The groups had similar complication rates over the 30-day follow-up, though SSIs were lower in the antibiotic group (1.6%) than the no antibiotic group (3.2%).

The researchers estimated that the number needed to treat for antibiotic therapy was 63 for SSIs, 83 for intra-abdominal SSI, and 125 for reintervention.

“Although longer preoperative antibiotic treatment resulted in slightly lower rate of postoperative infectious complications, the actual difference was very small and probably clinically not significant to justify longer preoperative antibiotic treatment,” Mentula and colleagues wrote.

 

Lower Infection Rates With Antibiotics

Commenting on the study for GI & Hepatology News, Theodore Pappas, MD, professor of surgery at Duke University School of Medicine in Durham, North Carolina, placed greater importance on these secondary outcomes.

Intra-abdominal infections, a subset of SSIs, were more than twice as common in the no-antibiotic group (1.9%) than in the antibiotic group (0.7%; P = .02). Positive blood cultures were also more common in the no-antibiotic group than the antibiotic group (P = .02).

While the authors qualified these results, “the reality was it was better to use antibiotics,” he said.

There was also a “big overlap between the two groups,” he said, which may have muted differences between the two groups. For example, one fourth of patients in the antibiotic group received only one dose of antibiotics, the same treatment regimen as the no-antibiotic group.

“Although protocol required prophylaxis in all patients in the induction of anesthesia, some clinicians thought that it was unnecessary, because antibiotics had already been given only a couple of hours ago” in patients in the antibiotic group, Mentula told GI & Hepatology News. She did not think that would affect the study’s results.

The PERFECT trial and the antibiotics subtrial answer two important questions that have been asked for years, Pappas continued: Whether appendectomy for uncomplicated acute appendicitis needs to be performed emergently and if antibiotics administered while waiting for surgery improve outcomes.

“Basically, the study shows that you probably should keep them on antibiotics while you’re waiting,” he said.

The study was funded by Finnish Medical Foundation, the Mary and Georg Ehrnrooth Foundation, the Biomedicum Helsinki Foundation, and The Norwegian Surveillance Programme for Antimicrobial Resistance and research funds from the Finnish government. Mentula received grants from the Finnish government during the conduct of the study and personal fees from Pfizer outside the submitted work. Pappas reported no relevant disclosures.

A version of this article appeared on Medscape.com.

Antibiotic treatment while awaiting appendectomy does not lower risk for appendiceal perforation in patients with uncomplicated acute appendicitis, according to a new study.

While the percentage of surgical site infections (SSIs) was small for both groups, patients who received antibiotics during the waiting period had lower rates of these infections.

The trial — titled PERFECT-Antibiotics — was a substudy embedded in a larger PERFECT clinical trial, which aimed to determine whether an in-hospital delay of appendectomy resulted in increased risk for appendiceal perforation when compared to emergent surgery.

The trial “concluded that appendectomy does not need to be performed promptly in acute uncomplicated appendicitis and can be scheduled within 24 hours without increasing complications,” senior author Panu Mentula, MD, of the Department of Gastroenterological Surgery, Helsinki University Hospital, Helsinki, Finland, and colleagues wrote in the study. “The next question is whether preoperatively started antibiotic treatment reduces the risk of appendiceal perforations.”

The findings were published online in JAMA Surgery on May 14, 2025.

 

Trial Design

PERFECT-Antibiotics was an open-label, randomized trial conducted at two hospitals in Finland and one hospital in Norway. Researchers enrolled 1774 individuals diagnosed with acute uncomplicated appendicitis, diagnosed clinically or via imaging. Patients were placed in one of two groups: The antibiotic group received intravenous (IV) cefuroxime (1500 mg) and metronidazole (500 mg) every 8 hours until surgery, while the nonantibiotic group waited for surgery without antibiotics.

All patients received one dose of IV cefuroxime (1500 mg) and metronidazole (500 mg) during anesthesia induction. The primary outcome was perforated appendicitis and secondary outcomes included complication rate and SSIs within 30 days of follow-up.

The median age of patients was 35 years (interquartile range [IQR], 28-46 years), and 55% of patients were men. Patients waited a median time of 9 hours (IQR, 4.3-15.5) from study randomization to undergoing surgery.

 

No Difference in Appendiceal Perforation

Of the 888 patients in the preoperative antibiotic group, 26.2% received one dose, 38.7% received two doses, 22.6% received three doses, and 11.8% received four or more doses of antibiotics, including the antibiotic dose given during anesthesia. A total of 74 patients (8.3%) in this group had a perforated appendix.

Of the 886 patients not given preoperative antibiotics, 79 (8.9%) had a perforated appendix, which met the predetermined noninferiority threshold.

The groups had similar complication rates over the 30-day follow-up, though SSIs were lower in the antibiotic group (1.6%) than the no antibiotic group (3.2%).

The researchers estimated that the number needed to treat for antibiotic therapy was 63 for SSIs, 83 for intra-abdominal SSI, and 125 for reintervention.

“Although longer preoperative antibiotic treatment resulted in slightly lower rate of postoperative infectious complications, the actual difference was very small and probably clinically not significant to justify longer preoperative antibiotic treatment,” Mentula and colleagues wrote.

 

Lower Infection Rates With Antibiotics

Commenting on the study for GI & Hepatology News, Theodore Pappas, MD, professor of surgery at Duke University School of Medicine in Durham, North Carolina, placed greater importance on these secondary outcomes.

Intra-abdominal infections, a subset of SSIs, were more than twice as common in the no-antibiotic group (1.9%) than in the antibiotic group (0.7%; P = .02). Positive blood cultures were also more common in the no-antibiotic group than the antibiotic group (P = .02).

While the authors qualified these results, “the reality was it was better to use antibiotics,” he said.

There was also a “big overlap between the two groups,” he said, which may have muted differences between the two groups. For example, one fourth of patients in the antibiotic group received only one dose of antibiotics, the same treatment regimen as the no-antibiotic group.

“Although protocol required prophylaxis in all patients in the induction of anesthesia, some clinicians thought that it was unnecessary, because antibiotics had already been given only a couple of hours ago” in patients in the antibiotic group, Mentula told GI & Hepatology News. She did not think that would affect the study’s results.

The PERFECT trial and the antibiotics subtrial answer two important questions that have been asked for years, Pappas continued: Whether appendectomy for uncomplicated acute appendicitis needs to be performed emergently and if antibiotics administered while waiting for surgery improve outcomes.

“Basically, the study shows that you probably should keep them on antibiotics while you’re waiting,” he said.

The study was funded by Finnish Medical Foundation, the Mary and Georg Ehrnrooth Foundation, the Biomedicum Helsinki Foundation, and The Norwegian Surveillance Programme for Antimicrobial Resistance and research funds from the Finnish government. Mentula received grants from the Finnish government during the conduct of the study and personal fees from Pfizer outside the submitted work. Pappas reported no relevant disclosures.

A version of this article appeared on Medscape.com.

Antibiotic treatment while awaiting appendectomy does not lower risk for appendiceal perforation in patients with uncomplicated acute appendicitis, according to a new study.

While the percentage of surgical site infections (SSIs) was small for both groups, patients who received antibiotics during the waiting period had lower rates of these infections.

The trial — titled PERFECT-Antibiotics — was a substudy embedded in a larger PERFECT clinical trial, which aimed to determine whether an in-hospital delay of appendectomy resulted in increased risk for appendiceal perforation when compared to emergent surgery.

The trial “concluded that appendectomy does not need to be performed promptly in acute uncomplicated appendicitis and can be scheduled within 24 hours without increasing complications,” senior author Panu Mentula, MD, of the Department of Gastroenterological Surgery, Helsinki University Hospital, Helsinki, Finland, and colleagues wrote in the study. “The next question is whether preoperatively started antibiotic treatment reduces the risk of appendiceal perforations.”

The findings were published online in JAMA Surgery on May 14, 2025.

 

Trial Design

PERFECT-Antibiotics was an open-label, randomized trial conducted at two hospitals in Finland and one hospital in Norway. Researchers enrolled 1774 individuals diagnosed with acute uncomplicated appendicitis, diagnosed clinically or via imaging. Patients were placed in one of two groups: The antibiotic group received intravenous (IV) cefuroxime (1500 mg) and metronidazole (500 mg) every 8 hours until surgery, while the nonantibiotic group waited for surgery without antibiotics.

All patients received one dose of IV cefuroxime (1500 mg) and metronidazole (500 mg) during anesthesia induction. The primary outcome was perforated appendicitis and secondary outcomes included complication rate and SSIs within 30 days of follow-up.

The median age of patients was 35 years (interquartile range [IQR], 28-46 years), and 55% of patients were men. Patients waited a median time of 9 hours (IQR, 4.3-15.5) from study randomization to undergoing surgery.

 

No Difference in Appendiceal Perforation

Of the 888 patients in the preoperative antibiotic group, 26.2% received one dose, 38.7% received two doses, 22.6% received three doses, and 11.8% received four or more doses of antibiotics, including the antibiotic dose given during anesthesia. A total of 74 patients (8.3%) in this group had a perforated appendix.

Of the 886 patients not given preoperative antibiotics, 79 (8.9%) had a perforated appendix, which met the predetermined noninferiority threshold.

The groups had similar complication rates over the 30-day follow-up, though SSIs were lower in the antibiotic group (1.6%) than the no antibiotic group (3.2%).

The researchers estimated that the number needed to treat for antibiotic therapy was 63 for SSIs, 83 for intra-abdominal SSI, and 125 for reintervention.

“Although longer preoperative antibiotic treatment resulted in slightly lower rate of postoperative infectious complications, the actual difference was very small and probably clinically not significant to justify longer preoperative antibiotic treatment,” Mentula and colleagues wrote.

 

Lower Infection Rates With Antibiotics

Commenting on the study for GI & Hepatology News, Theodore Pappas, MD, professor of surgery at Duke University School of Medicine in Durham, North Carolina, placed greater importance on these secondary outcomes.

Intra-abdominal infections, a subset of SSIs, were more than twice as common in the no-antibiotic group (1.9%) than in the antibiotic group (0.7%; P = .02). Positive blood cultures were also more common in the no-antibiotic group than the antibiotic group (P = .02).

While the authors qualified these results, “the reality was it was better to use antibiotics,” he said.

There was also a “big overlap between the two groups,” he said, which may have muted differences between the two groups. For example, one fourth of patients in the antibiotic group received only one dose of antibiotics, the same treatment regimen as the no-antibiotic group.

“Although protocol required prophylaxis in all patients in the induction of anesthesia, some clinicians thought that it was unnecessary, because antibiotics had already been given only a couple of hours ago” in patients in the antibiotic group, Mentula told GI & Hepatology News. She did not think that would affect the study’s results.

The PERFECT trial and the antibiotics subtrial answer two important questions that have been asked for years, Pappas continued: Whether appendectomy for uncomplicated acute appendicitis needs to be performed emergently and if antibiotics administered while waiting for surgery improve outcomes.

“Basically, the study shows that you probably should keep them on antibiotics while you’re waiting,” he said.

The study was funded by Finnish Medical Foundation, the Mary and Georg Ehrnrooth Foundation, the Biomedicum Helsinki Foundation, and The Norwegian Surveillance Programme for Antimicrobial Resistance and research funds from the Finnish government. Mentula received grants from the Finnish government during the conduct of the study and personal fees from Pfizer outside the submitted work. Pappas reported no relevant disclosures.

A version of this article appeared on Medscape.com.

A new study adds to what has been emerging in the literature — namely that there appear to be gut microbiome “signatures” for various pain conditions — suggesting that microbiome-based diagnostics and therapeutics may one day be routine for a broad range of pain conditions.

“There is now a whole list of pain conditions that appear to have these signatures, including postoperative pain, arthritis, neuropathy and migraine to name a few,” Robert Bonakdar, MD, director of pain management, Scripps Center for Integrative Medicine, San Diego, told GI & Hepatology News.

Fibromyalgia and complex regional pain syndrome (CRPS) are also on the list.

A team led by Amir Minerbi, MD, PhD, director of the Institute for Pain Medicine, Haifa, Israel, and colleagues published one of the first articles on gut changes in fibromyalgia. They noted that the gut microbiome could be utilized to determine which individuals had the condition and which did not — with about a 90% accuracy.

The team went on to show that transplanting gut microbiota from patients with fibromyalgia into germ-free mice was sufficient to induce pain-like behaviors in the animals — “effects that were reversed when healthy human microbiota were transplanted instead,” Minerbi told GI & Hepatology News.

Further, in a pilot clinical study, the researchers showed that transplanting microbiota from healthy donors led to a reduction in pain and other symptoms in women with treatment-resistant fibromyalgia.

Most recently, they found significant differences in the composition of the gut microbiome in a cohort of patients with CRPS from Israel, compared to matched pain-free control individuals.

Notably, two species — Dialister succinatiphilus and Phascolarctobacterium faecium – were enriched in patients with CRPS, while three species — Ligilactobacillus salivarius, Bifidobacterium dentium, and Bifidobacterium adolescentis – were increased in control samples, according to their report published last month in Anesthesiology.

“Importantly,” these findings were replicated in an independent cohort of patients with CRPS from Canada, “suggesting that the observed microbiome signature is robust and consistent across different environments,” Minerbi told GI & Hepatology News.

 

Causal Role? 

“These findings collectively suggest a causal role for the gut microbiome in at least some chronic pain conditions,” Minerbi said.

However, the co-authors of a linked editorial cautioned that it’s “unclear if D succinatiphilus or P faecium are functionally relevant to CRPS pathophysiology or if the bacteria increased in healthy control samples protect against CRPS development.”

Minerbi and colleagues also observed that fecal concentrations of all measured short chain fatty acids (SCFA) in patients with CRPS were lower on average compared to pain-free control individuals, of which butyric, hexanoic, and valeric acid showed significant depletion.

Additionally, plasma concentrations of acetic acid showed significant depletion in patients with CRPS vs control individuals, while propionate, butyrate, isobutyrate and 2-methyl-butyric acid showed a trend toward lower concentrations.

The quantification of SCFA in patient stool and serum is a “notable advance” in this study, Zulmary Manjarres, PhD; Ashley Plumb, PhD; and Katelyn Sadler, PhD; with the Center for Advanced Pain Studies at The University of Texas at Dallas, wrote in their editorial.

SCFA are produced by bacteria as a byproduct of dietary fiber fermentation and appropriate levels of these compounds are important to maintain low levels of inflammation in the colon and overall gut health, they explained.

This begs the question of whether administering probiotic bacteria — many of which are believed to exert health benefits through SCFA production — can be used to treat CRPS-associated pain. It’s something that needs to be studied, the editorialists wrote.

Yet, in their view, the “most notable achievement” of Minerbi and colleagues is the development of a machine learning model that accurately, specifically and sensitively categorized individuals as patients with CRPS or control individuals based on their fecal microbiome signature.

The model, trained on exact sequence variant data from the Israeli patients, achieved 89.5% accuracy, 90.0% sensitivity, and 88.9% specificity in distinguishing patients with CRPS from control individuals in the Canadian cohort.

Interestingly, in three patients with CRPS who underwent limb amputation and recovered from their pain, their gut microbiome signature remained unchanged, suggesting that microbiome alterations might precede or persist beyond symptomatic phases.

 

Test and Treat: Are We There Yet? 

The gut microbiome link to chronic pain syndromes is a hot area of research, but for now gut microbial testing followed by treatment aimed at “fixing” the microbiome remains largely experimental.

At this point, comprehensive gut-microbiome sequencing is not a routine, guideline-supported part of care for fibromyalgia or any chronic pain condition.

“Unfortunately, even for doctors interested in this area, we are not quite at the state of being able to diagnose and treat pain syndrome based on microbiome data,” Bonakdar told GI & Hepatology News.

He said there are many reasons for this including that this type of microbiome analysis is not commonly available at a routine lab. If patients do obtain testing, then the results are quite complex and may not translate to a diagnosis or a simple microbiome intervention.

“I think the closest option we have now is considering supplementing with commonly beneficial probiotic in pain conditions,” Bonakdar said.

One example is a preliminary fibromyalgia trial which found that supplementing with Lactobacillus, Bifidobacterium, and Saccharomyces boulardii appeared to have benefit.

“Unfortunately, this is hit or miss as other trials such as one in low back pain did not find benefit,” Bonakdar said.

Addressing gut microbiome changes will become “more actionable when microbiome analysis is more commonplace as well as is the ability to tailor treatment to the abnormalities seen on testing in a real-world manner,” Bonakdar said.

“Until then, there is no harm in promoting an anti-inflammatory diet for our patients with pain which we know can improve components of the microbiome while also supporting pain management,” he concluded.

Minerbi, Bonakdar, and the editorial writers had no relevant disclosures.

A version of this article appeared on Medscape.com.

A new study adds to what has been emerging in the literature — namely that there appear to be gut microbiome “signatures” for various pain conditions — suggesting that microbiome-based diagnostics and therapeutics may one day be routine for a broad range of pain conditions.

“There is now a whole list of pain conditions that appear to have these signatures, including postoperative pain, arthritis, neuropathy and migraine to name a few,” Robert Bonakdar, MD, director of pain management, Scripps Center for Integrative Medicine, San Diego, told GI & Hepatology News.

Fibromyalgia and complex regional pain syndrome (CRPS) are also on the list.

A team led by Amir Minerbi, MD, PhD, director of the Institute for Pain Medicine, Haifa, Israel, and colleagues published one of the first articles on gut changes in fibromyalgia. They noted that the gut microbiome could be utilized to determine which individuals had the condition and which did not — with about a 90% accuracy.

The team went on to show that transplanting gut microbiota from patients with fibromyalgia into germ-free mice was sufficient to induce pain-like behaviors in the animals — “effects that were reversed when healthy human microbiota were transplanted instead,” Minerbi told GI & Hepatology News.

Further, in a pilot clinical study, the researchers showed that transplanting microbiota from healthy donors led to a reduction in pain and other symptoms in women with treatment-resistant fibromyalgia.

Most recently, they found significant differences in the composition of the gut microbiome in a cohort of patients with CRPS from Israel, compared to matched pain-free control individuals.

Notably, two species — Dialister succinatiphilus and Phascolarctobacterium faecium – were enriched in patients with CRPS, while three species — Ligilactobacillus salivarius, Bifidobacterium dentium, and Bifidobacterium adolescentis – were increased in control samples, according to their report published last month in Anesthesiology.

“Importantly,” these findings were replicated in an independent cohort of patients with CRPS from Canada, “suggesting that the observed microbiome signature is robust and consistent across different environments,” Minerbi told GI & Hepatology News.

 

Causal Role? 

“These findings collectively suggest a causal role for the gut microbiome in at least some chronic pain conditions,” Minerbi said.

However, the co-authors of a linked editorial cautioned that it’s “unclear if D succinatiphilus or P faecium are functionally relevant to CRPS pathophysiology or if the bacteria increased in healthy control samples protect against CRPS development.”

Minerbi and colleagues also observed that fecal concentrations of all measured short chain fatty acids (SCFA) in patients with CRPS were lower on average compared to pain-free control individuals, of which butyric, hexanoic, and valeric acid showed significant depletion.

Additionally, plasma concentrations of acetic acid showed significant depletion in patients with CRPS vs control individuals, while propionate, butyrate, isobutyrate and 2-methyl-butyric acid showed a trend toward lower concentrations.

The quantification of SCFA in patient stool and serum is a “notable advance” in this study, Zulmary Manjarres, PhD; Ashley Plumb, PhD; and Katelyn Sadler, PhD; with the Center for Advanced Pain Studies at The University of Texas at Dallas, wrote in their editorial.

SCFA are produced by bacteria as a byproduct of dietary fiber fermentation and appropriate levels of these compounds are important to maintain low levels of inflammation in the colon and overall gut health, they explained.

This begs the question of whether administering probiotic bacteria — many of which are believed to exert health benefits through SCFA production — can be used to treat CRPS-associated pain. It’s something that needs to be studied, the editorialists wrote.

Yet, in their view, the “most notable achievement” of Minerbi and colleagues is the development of a machine learning model that accurately, specifically and sensitively categorized individuals as patients with CRPS or control individuals based on their fecal microbiome signature.

The model, trained on exact sequence variant data from the Israeli patients, achieved 89.5% accuracy, 90.0% sensitivity, and 88.9% specificity in distinguishing patients with CRPS from control individuals in the Canadian cohort.

Interestingly, in three patients with CRPS who underwent limb amputation and recovered from their pain, their gut microbiome signature remained unchanged, suggesting that microbiome alterations might precede or persist beyond symptomatic phases.

 

Test and Treat: Are We There Yet? 

The gut microbiome link to chronic pain syndromes is a hot area of research, but for now gut microbial testing followed by treatment aimed at “fixing” the microbiome remains largely experimental.

At this point, comprehensive gut-microbiome sequencing is not a routine, guideline-supported part of care for fibromyalgia or any chronic pain condition.

“Unfortunately, even for doctors interested in this area, we are not quite at the state of being able to diagnose and treat pain syndrome based on microbiome data,” Bonakdar told GI & Hepatology News.

He said there are many reasons for this including that this type of microbiome analysis is not commonly available at a routine lab. If patients do obtain testing, then the results are quite complex and may not translate to a diagnosis or a simple microbiome intervention.

“I think the closest option we have now is considering supplementing with commonly beneficial probiotic in pain conditions,” Bonakdar said.

One example is a preliminary fibromyalgia trial which found that supplementing with Lactobacillus, Bifidobacterium, and Saccharomyces boulardii appeared to have benefit.

“Unfortunately, this is hit or miss as other trials such as one in low back pain did not find benefit,” Bonakdar said.

Addressing gut microbiome changes will become “more actionable when microbiome analysis is more commonplace as well as is the ability to tailor treatment to the abnormalities seen on testing in a real-world manner,” Bonakdar said.

“Until then, there is no harm in promoting an anti-inflammatory diet for our patients with pain which we know can improve components of the microbiome while also supporting pain management,” he concluded.

Minerbi, Bonakdar, and the editorial writers had no relevant disclosures.

A version of this article appeared on Medscape.com.

A new study adds to what has been emerging in the literature — namely that there appear to be gut microbiome “signatures” for various pain conditions — suggesting that microbiome-based diagnostics and therapeutics may one day be routine for a broad range of pain conditions.

“There is now a whole list of pain conditions that appear to have these signatures, including postoperative pain, arthritis, neuropathy and migraine to name a few,” Robert Bonakdar, MD, director of pain management, Scripps Center for Integrative Medicine, San Diego, told GI & Hepatology News.

Fibromyalgia and complex regional pain syndrome (CRPS) are also on the list.

A team led by Amir Minerbi, MD, PhD, director of the Institute for Pain Medicine, Haifa, Israel, and colleagues published one of the first articles on gut changes in fibromyalgia. They noted that the gut microbiome could be utilized to determine which individuals had the condition and which did not — with about a 90% accuracy.

The team went on to show that transplanting gut microbiota from patients with fibromyalgia into germ-free mice was sufficient to induce pain-like behaviors in the animals — “effects that were reversed when healthy human microbiota were transplanted instead,” Minerbi told GI & Hepatology News.

Further, in a pilot clinical study, the researchers showed that transplanting microbiota from healthy donors led to a reduction in pain and other symptoms in women with treatment-resistant fibromyalgia.

Most recently, they found significant differences in the composition of the gut microbiome in a cohort of patients with CRPS from Israel, compared to matched pain-free control individuals.

Notably, two species — Dialister succinatiphilus and Phascolarctobacterium faecium – were enriched in patients with CRPS, while three species — Ligilactobacillus salivarius, Bifidobacterium dentium, and Bifidobacterium adolescentis – were increased in control samples, according to their report published last month in Anesthesiology.

“Importantly,” these findings were replicated in an independent cohort of patients with CRPS from Canada, “suggesting that the observed microbiome signature is robust and consistent across different environments,” Minerbi told GI & Hepatology News.

 

Causal Role? 

“These findings collectively suggest a causal role for the gut microbiome in at least some chronic pain conditions,” Minerbi said.

However, the co-authors of a linked editorial cautioned that it’s “unclear if D succinatiphilus or P faecium are functionally relevant to CRPS pathophysiology or if the bacteria increased in healthy control samples protect against CRPS development.”

Minerbi and colleagues also observed that fecal concentrations of all measured short chain fatty acids (SCFA) in patients with CRPS were lower on average compared to pain-free control individuals, of which butyric, hexanoic, and valeric acid showed significant depletion.

Additionally, plasma concentrations of acetic acid showed significant depletion in patients with CRPS vs control individuals, while propionate, butyrate, isobutyrate and 2-methyl-butyric acid showed a trend toward lower concentrations.

The quantification of SCFA in patient stool and serum is a “notable advance” in this study, Zulmary Manjarres, PhD; Ashley Plumb, PhD; and Katelyn Sadler, PhD; with the Center for Advanced Pain Studies at The University of Texas at Dallas, wrote in their editorial.

SCFA are produced by bacteria as a byproduct of dietary fiber fermentation and appropriate levels of these compounds are important to maintain low levels of inflammation in the colon and overall gut health, they explained.

This begs the question of whether administering probiotic bacteria — many of which are believed to exert health benefits through SCFA production — can be used to treat CRPS-associated pain. It’s something that needs to be studied, the editorialists wrote.

Yet, in their view, the “most notable achievement” of Minerbi and colleagues is the development of a machine learning model that accurately, specifically and sensitively categorized individuals as patients with CRPS or control individuals based on their fecal microbiome signature.

The model, trained on exact sequence variant data from the Israeli patients, achieved 89.5% accuracy, 90.0% sensitivity, and 88.9% specificity in distinguishing patients with CRPS from control individuals in the Canadian cohort.

Interestingly, in three patients with CRPS who underwent limb amputation and recovered from their pain, their gut microbiome signature remained unchanged, suggesting that microbiome alterations might precede or persist beyond symptomatic phases.

 

Test and Treat: Are We There Yet? 

The gut microbiome link to chronic pain syndromes is a hot area of research, but for now gut microbial testing followed by treatment aimed at “fixing” the microbiome remains largely experimental.

At this point, comprehensive gut-microbiome sequencing is not a routine, guideline-supported part of care for fibromyalgia or any chronic pain condition.

“Unfortunately, even for doctors interested in this area, we are not quite at the state of being able to diagnose and treat pain syndrome based on microbiome data,” Bonakdar told GI & Hepatology News.

He said there are many reasons for this including that this type of microbiome analysis is not commonly available at a routine lab. If patients do obtain testing, then the results are quite complex and may not translate to a diagnosis or a simple microbiome intervention.

“I think the closest option we have now is considering supplementing with commonly beneficial probiotic in pain conditions,” Bonakdar said.

One example is a preliminary fibromyalgia trial which found that supplementing with Lactobacillus, Bifidobacterium, and Saccharomyces boulardii appeared to have benefit.

“Unfortunately, this is hit or miss as other trials such as one in low back pain did not find benefit,” Bonakdar said.

Addressing gut microbiome changes will become “more actionable when microbiome analysis is more commonplace as well as is the ability to tailor treatment to the abnormalities seen on testing in a real-world manner,” Bonakdar said.

“Until then, there is no harm in promoting an anti-inflammatory diet for our patients with pain which we know can improve components of the microbiome while also supporting pain management,” he concluded.

Minerbi, Bonakdar, and the editorial writers had no relevant disclosures.

A version of this article appeared on Medscape.com.

Dear Friends,

Like many readers, I just returned from Digestive Disease Week® (DDW) in San Diego, California. For the first time in my early career, my experience was not just overwhelming and exhausting. Before, I wanted to do everything – lectures, posters, meetings with friends, prospective research collaborators, and more! This year, I acknowledged that instead of spreading myself thin and not fully engaging, I made a focused daily schedule mixed with productivity and social events, selecting only what was most important to me at this time in my career. This time, after DDW, instead of giving in to my inner introvert and holing myself in my house for a week to recover, I am invigorated by what I learned and the people I met. I can’t wait to see what’s to come next year!

In this issue’s “In Focus”, Dr. Evan Dellon describes his diagnostic approach, including a clear history, endoscopic evaluation with biopsy, and ruling out other causes of esophageal eosinophilia. He emphasizes that treatment should target both inflammation and fibrostenosis and reviews the guidelines and evidence behind first-line treatments, surveillance, and long-term maintenance.

In the second of a two-part series in the “Short Clinical Review” section, Dr. Christopher Vélez, Dr. Rosa L. Yu, and Dr. Jennifer Dimino discuss care for patients with disorders of brain-gut interaction from historically marginalized communities. They highlight ways to improve care for these patients in day-to-day clinical practice.

The transition from trainee to a practicing gastroenterologist may bring with it responsibilities of giving feedback to trainees and/or colleagues to improve. In the “Early Career” section, Dr. Michelle Baliss and Dr. Christine Hachem give practical tips on how best to deliver feedback, with a focus on creating time, building rapport, bidirectional communication, and more.

Lastly, in the “Finance/Legal” section, John S. Gardner, a financial advisor, guides trainees and early career gastroenterologists through estate planning – why it’s important, how to do it effectively, and long-term benefits to starting early.

If you are interested in contributing or have ideas for future TNG topics, please contact me (tjudy@wustl.edu) or Danielle Kiefer (dkiefer@gastro.org), Communications/Managing Editor of TNG.

Until next time, I leave you with a historical fun fact because we would not be where we are now without appreciating where we were: the first case of eosinophilic esophagitis was only first described in 1978 and became a distinct entity in the early 1990s.

Yours truly, 

Judy A. Trieu, MD, MPH

Editor-in-Chief

Assistant Professor of Medicine

Interventional Endoscopy, Division of Gastroenterology

Washington University School of Medicine in St. Louis