Microbiome Makeover: Out With the Bad, In With the Good?

Digestive Disease Week (DDW) 2018

William F. Balistreri, MD


August 08, 2018

In This Article

An increasing body of experimental data strongly indicate that the gut microbiome, the trillions of microbes that colonize the gut of an individual, strongly influences both health and disease. Our microflora carry out essential functions; they facilitate digestion, generate needed nutrients via microbial metabolic activities, mediate brain-gut communication, modulate host immune responses, and harvest energy from food.[1] Host-bacteria interactions not only influence normal physiology but also may induce susceptibility to disease; disruption of the symbiosis between microbiota and host (dysbiosis) may have profound untoward effects. Alterations in the balance between harmful bacteria and beneficial bacteria have been associated with such disorders as irritable bowel syndrome (IBS), inflammatory bowel disease, obesity, malnutrition, and liver diseases. An increasing understanding of the link between compositional and functional changes of the microbiota have led to innovative diagnostic techniques and development of novel therapies.

Studies presented at this year's Digestive Disease Week (DDW) addressed the role of the microbiome in the development and treatment of IBS as well as other gastrointestinal disorders.

Intestinal Microbiota as Mediator and Marker of IBS

Although disruption of the gut microflora has been implicated in the genesis and perpetuation of symptoms in patients with IBS, this complex is poorly characterized.

Hollister and colleagues[2] hypothesized that specific microbial factors were associated with the frequency and severity of abdominal pain in patients with IBS and, furthermore, that fecal microbial signatures and fecal metabolites would differentiate those with IBS from healthy controls. They used a comprehensive phenotyping and multiomic strategy (whole-genome shotgun sequencing and global fecal metabolomics) to examine samples from patients with IBS-related abdominal pain. Patients with IBS were distinguishable from healthy controls by intestinal microbes (eg, Flavonifractor plautiii and Lachnospiraceae bacterium), microbial genes/pathways, and fecal metabolites. Microbial multiomic factors also appeared to directly correlate with IBS-associated pain. These findings may lead to new IBS microbiome-based diagnostic and therapeutic strategies.

Brain-Gut-Microbiome Axis

There is a growing recognition that bidirectional signals between the digestive tract and the central nervous system play an important role in symptom generation in patients with IBS; these signals may influence the response to various therapeutic interventions.

Jacobs and colleagues[3] presented a large randomized controlled trial finding that cognitive-behavioral therapy (CBT) reduces symptoms in patients with IBS as assessed by the IBS-SSS (symptom severity score). They postulated that the efficacy of this centrally directed intervention is influenced by the brain-gut-microbiome axis, and that the composition of the gut microbiome may predict the response.

To investigate the baseline state of the gut microbiome, and whether CBT altered the composition and function of the microbiome, they collected stool samples from patients with IBS at baseline and 12 weeks after randomization to clinic-based CBT, home-based CBT, or patient education only (control). Baseline microbiome composition was significantly associated with response, defined as a > 50 point decrease in the IBS-SSS, in both CBT-treated patient groups at the end of treatment but not in the control group. Patients responding to CBT had increased fecal serotonin levels compared with nonresponders.

The association of pretreatment intestinal microbiota with the response to CBT suggests that peripheral signals from the microflora may modulate central processes that generate symptoms in patients with IBS; these are influenced by CBT. Alternatively, the microbiota may reflect disturbed top-down signals from the brain that affect gut function and that may be modified by CBT.

These results emphasize the need for mechanistic investigation into differences in the brain-gut-microbiome axis between patients with IBS with CBT-responsive and nonresponsive microbiota.


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