Irritable bowel syndrome (IBS) is a chronic functional gastrointestinal disorder that
generates a significant health care burden and is the most commonly diagnosed
gastrointestinal condition. Nearly 12% of all patients in the United States seek medical care
in primary care practice for IBS and it accounts for 3.1 million ambulatory care visits and
5.9 million prescriptions annually.
The pathophysiology of IBS is distinctly broad compared to other gastrointestinal conditions
and includes abnormalities involving motility, visceral sensation, brain-gut interaction, and
distress. Though patients with IBS often have a heterogeneous symptom profile, the
predominant theme is the presence of abdominal pain or discomfort that is usually relieved by
defecation. Host factors such as genetics, immune function, and psychological status, as well
as environmental factors such as stress, recent infection, or treatment with antibiotics,
could predispose to the development of chronic IBS symptoms. Due to a myriad of contributing
factors, a single cause of IBS remains enigmatic. Despite the urgent need to develop better
therapies, the high range of placebo response has made clinical trials challenging, ranging
from 16.0 to 71.4% with a population-weighted average of 40.2%.
Recent studies have also shown alterations in gut immune response, and a disrupted intestinal
and colonic microbiome in association with IBS. The current working hypothesis is that
abnormal microbiota activate mucosal innate immune responses, which increase epithelial
permeability, activate nociceptive sensory pathways, and dysregulate the enteric nervous
system. Targeting the microbiota and gastrointestinal tract with live organisms is a
promising approach, yet previous trials have yielded limited success due to empiric strain
selection, small population size, and inadequate trial design to control for a high placebo
response.
This protocol aims to assess the impact of a multi-strain consortia of 24 commensal organisms
across 12 species with extensive strain-specific in vivo data, assessing a range of
gastrointestinal symptoms without negatively altering the naive gut microbiota.
High-throughput shotgun DNA sequencing will provide opportunity for '-omics'-based analyses
of the gut microbiota, which can be augmented by the metabolite profiles resulting from total
microbial activity in the gut. Since many of these metabolites are bioeffector molecules
acting upon the host, such analysis can provide a direct measure of the consequences of
microbial activity in the gut and provide a novel integrated data set for patients with IBS.
Recruited subjects will also use a smart-phone application to report day to day
gastrointestinal symptoms, a patient-centric hallmark of this chronic gut condition.
Probiotics are live microorganisms with a vast array of therapeutic potential for
gastrointestinal disease. Several probiotics strains have shown beneficial outcomes in
constipation-predominant IBS (IBS-C) patients, especially as an adjunct to conventional
treatment. However, a number of controversial issues regarding the roles of probiotics in
pathogenesis of IBS-C remain to be clarified, including precise mechanism of action.
This protocol aims to assess the impact of a mix of 24-beneficial strains on individual
gastrointestinal symptoms specifically in a cohort of subjects with IBS-C or IBS-M.