Gut microbiome characteristics predict treatment response in IBS-D patients

In a new study published in Clinical Gastroenterology and Hepatology, the low FODMAP diet and the antibiotic rifaximin provided similar and significant relief for patients with irritable bowel syndrome with diarrhea (IBS-D). 

Researchers also observed distinct characteristics of patients' gut microbiomes that predicted whether they responded to the low FODMAP diet or rifaximin - or did not respond to treatment. 

Importantly, we found that differences in the gut microbiome may help predict which patients respond to specific therapies."

Allen Lee, M.D., M.S., Assistant Professor of Internal Medicine at the University of Michigan Medical School and lead author of the paper

"We also identified a distinct microbial signature among patients who did not respond to either treatment, suggesting that it may be possible to identify non-responders to common microbiome-based therapies, such as rifaximin and the low FODMAP diet, before starting treatment." 

Irritable bowel syndrome affects 10% to 15% of adults in the United States and is characterized by symptoms such as abdominal pain, bloating and altered bowel habits. 

The low FODMAP diet is a proven therapy involving the elimination of foods containing certain carbohydrates. 

Still, the low FODMAP diet and rifaximin are each effective in fewer than half of patients. 

In addition to comparing low FODMAP diet and rifaximin, the researchers aimed to investigate the possibility that gut microbial testing could one day allow for more precise treatment recommendations. 

"Right now, treating IBS often involves a trial-and-error approach, where patients cycle through therapies before finding one that works. This can be frustrating, time-consuming, and burdensome for patients," Lee said. 

"Our study was motivated by emerging evidence that the gut microbiome plays a key role in IBS, and that these microbial differences may help explain why some patients respond to certain treatments while others do not. By better understanding these patterns, we hope to move toward a personalized approach to care." 

In this single-center, randomized controlled trial, 65 subjects were assigned to either a 14-day course of rifaximin or low FODMAP diet counseling. 

After five weeks, both groups achieved comparable and significant decreases in abdominal pain and bloating. 

Meanwhile, stool samples were collected at weeks 0, 2, 4, and 5 for analysis of the participants' gut microbiomes. 

Researchers were able to analyze whether specific bacteria predicted treatment response, as well as how different microbiome characteristics corresponded to the improvement of different symptoms. 

(Breath tests were also performed but found to be ineffective at predicting treatment response.) 

Among their findings was that patients who responded to the low FODMAP diet had lower baseline abundance of putative saccharolytic taxa and demonstrated increases in microbial diversity over time. 

The rifaximin responders, meanwhile, were enriched in taxa with potential short-chain fatty acid-producing and bile acid-modifying capabilities, suggesting a microbial community more resilient to antibiotic exposure. 

Notably, patients who did not respond to either therapy were enriched in putative proteolytic taxa, highlighting a distinct microbial profile associated with treatment resistance. 

Ultimately, the researchers emphasize that findings are "hypothesis-generating rather than definitive." 

They hope future validation will lead to more personalized clinical therapy.