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    • Studies on FXR knockout mice demonstrated that FXR activity

    2021-11-22

    Studies on FXR knockout mice demonstrated that FXR activity is necessary to maintain a proper integrity of intestinal tight junction [18]. HF diet-induced bowel dysfunction impaired FXR activity and affected fecal BA profile. Generally, it augmented the concentration of secondary BAs in the colon e.g. DCA, which substantially disrupted the gut barrier function [60]. A HF diet increased the fecal concentration of DCA, LCA, CA, α-MCA, CDCA and hyodeoxycholic bafilomycin a1 in mice and simultaneously reduced the amount of UDCA, which is potentially cytoprotective. [60] Decreased fecal content of UDCA was correlated with increased intestinal permeability [61]. On the contrary, orally administered UDCA stabilized lipid bilayers and exhibited barrier-protective effects which counteracted the DCA-induced disruption of the colonic epithelium [60]. It has also been shown that UDCA was able to attenuate the severity of chemically-induced colitis and colitis-associated adenocarcinoma in vivo [62]. Available data on differences in dietary fat intake between IBS patients and controls are rather subjective reports of patients and are usually inconsistent. Some failed to detect any differences in the profile of fat intake, while others observed an increased intake of fat and saturated FAs in IBS patients. The latest findings from the cohort study, evaluating differences in food consumption and nutrient intake in subjects with IBS showed that IBS patients tended to consume higher amount of fats when compared to healthy controls [63]. A large proportion of IBS patients reported worsening of symptoms which was related to exacerbated colonic response to lipids. It has been shown that patients with IBS-D, who consume high-fat products, synthesize and excrete higher levels of CDCA and DCA, compared with controls [64], which may explain accelerated colonic transit among these subjects [65]. Patients with FGIDs are much more sensitive to small intestinal lipid exposure, which induces symptoms of fullness, bloating and nausea, than healthy controls. They are also more likely to report an increased intestinal sensitivity to mechanical distension, an effect mediated, at least in part, by sensitization of gut mechanoreceptors. In response to the supply of lipids or fatty meal, various peptide hormones, including cholecystokinin (CCK), are released, which mediate intestinal motility and perception [66]. CCK causes smooth muscle contractions of the digestive tract and accelerates GI motility contributing to diarrhea [67]. In order to improve quality of life and reduce symptoms, many patients with IBS follow the diet low in FODMAP [68]. FODMAPs are fermentable oligosaccharides, disaccharides, monosaccharides and polyols able to pass unabsorbed to the colon. During the fermentation process FODMAP-derived metabolites induce gas production, which causes luminal distension, increase in intraluminal tension, abdominal bloating and pain [33]. A significant amount of gases in turn can contribute to increased intestinal permeability and (low-grade) inflammatory response [68]. Diet low in FODMAP reduces major symptoms experienced by IBS patients [56], [57], [69]. Patients on FODMAP diet frequently observe changes in fecal pH that occur as a result of reduction of total bacteria count, such as prebiotic bacteria, Akkermansia muciniphila or Ruminococcus gnavus and particularly decrease in butyrate-producing bacteria [70]. Anaerobic intestinal bacteria and dietary fibers contribute to the formation of short-chain fatty acids (SCFAs) which affect lipid metabolism by controlling FA synthesis through the action of 5′ AMP-activated protein kinase and FXR [71]. Recent findings reported by Sherwin et al., showed that the impaired quality of life in individuals with IBS may be associated with their body weight [72]. The authors concluded that their outcomes present a worrisome outlook for IBS patients who are overweight or have increased body fat. It is thus conceivable that those overweight IBS individuals incorporate a dietary regimen in their daily routine to help them reduce the calorie intake and thereby fight the symptoms they experience.