**5.5 Irritable bowel syndrome**

Irritable bowel syndrome (IBS) is classified as a functional gastrointestinal disease [114]. Prevalence rates worldwide are around 11% with impact on younger patients. For this reason, there is a significant economic and sociologic burden associated with this disease. This has amounted to around \$20 billion per year in direct and indirect costs to the U.S. Economy [115]. The pathophysiology of IBS involves changes in the gut microbiota, malabsorption of bile acid, and changes to the enteric nervous system. Prior metanalyses have found that probiotics demonstrate improved overall symptom response and pain [116, 117].

One particular strain, *Bifidobacterium bifidum* MIMBb75, was found in a randomized control study by Guglielmetti et al. to cause a significant reduction in global assessment of IBS by −0.88 points (95% CI: −1.07; −0.69) when compared with only −0.16 (95% CI: −0.32; 0.00) points in the placebo group (P < 0.0001) with excellent tolerability and no difference in adverse events [118]. Andresen et al. replicated this result using a heat-inactivated *Bifidobacterium bifidum* MIMBb75 (SYN-HI-001) in a

high-powered study finding that the beneficial bacterial effects of this strain on IBS were independent of bacteria viability [119].

The metabolites of microbiota often include bile acid (BA), which has been attributed to IBS symptoms. BAs are released in the duodenum after conjugation in the liver, which are then made into secondary BAs by gut bacteria. BAs can have prosecretory effects that can regulate gut motility and impact gut sensitivity [120]. BAs are impacted by bacteria in the gut and impact the gut themselves, thus it is thought they may impact IBS. Patients with IBS have been reported to have changes in their microbial profiles. For example, there has been a significant increase in fecal primary BA and a decrease in secondary BA in patients with IBS-predominant diarrhea. There has also been a direct positive correlation between primary BA and IBS symptoms. In IBS with predominant diarrhea, there has been an observed reduction in bacteria from genera *Ruminococcaceae* and a negative correlation with primary BAs. There seems to be a definite connection between BAs and IBS, which will need to be further investigated [120].

Overall, the quality of the evidence behind the use in IBS remains weak. Indeed, the ACG states that there is very low evidence for the use of probiotics in IBS, which has resulted in a weak recommendation for their use in IBS. The AGA shares this sentiment and makes no recommendation for the use of probiotics in IBS [121]. This weak recommendation is justified given significant heterogeneity between studies, publication bias, and small sample size studies. This being said, the ACG does acknowledge that when probiotics are studied as a group, they improve bloating and the flatulence in IBS patients [121]. While there has been no broad recommendation for the use of probiotics in IBS. There is evidence that they make a difference and are of continued interest among patients and providers.

### **5.6 Probiotics in the critically ill**

There is growing evidence that probiotics may reduce the rate of the ventilatorassociated pneumonia (VAP), overall infection rate, nosocomial pneumonia, duration of mechanical ventilation, and antibiotic use for critically ill patients. VAP is considered the second most common nosocomial infection in the U.S. imposing a significant economic burden. While the American Thoracic Society (ATS) makes recommendations on the prophylaxis of the VAP in patients in the ICU typically involving antibiotics, the prospect of probiotics is compelling [122, 123]. Probiotics have also been used in patients with pancreatitis in the ICU. A meta-analysis analyzing 13 studies with N = 1188 found a statistically significant decrease in the length of ICU stay when probiotics were administered [124]. While no study has been able to find any effect on probiotics and length of hospital stay or mortality, there is convincing evidence that the flora may impact the outcomes of the critically ill patients. Like most areas of probiotics research, more detailed research needs to be done on how specific strains impact specific problems experienced by the patient.
