The current gold standard for diagnosing

The current gold standard for diagnosing BAM or BAD is the measurement of BA turnover rate with radiolabelled tauroselcholic (75selenium) Epinephrine Bitartrate synthesis (also known as the SeHCAT retention test). SeHCAT test involves the use of a synthetic analogue of naturally occurring conjugated taurocholic acid and measurement of 75SeHCAT retention by external scintigraphy (gamma camera) at 3 h and 7 days following oral administration of the gamma-emitter (in a form of capsule) [24], [25]. Several compounds have been identified so far as potential FXR ligands with different binding affinity, including endogenous BAs, synthetic agonists as well as steroids, aromatics or fatty acids [26]. FXR can be also directly stimulated through the release of bioactive substances secreted by Bacteroides dorei and Eubacterium limosum in the gut [27]. The presence of specific strains of gut microbiota can thus increase the production of more hydrophobic secondary BA metabolites and impact the BA profile via FXR [28]. In line, tauro-β-muricholic acid (TβMCA) is an example of a competitive FXR antagonist, which affects FXR signaling causing changes in host metabolism [5], [29]. Recent studies have also identified tauro-α-muricholic acid (TαMCA) as another FXR antagonist [30]. Studies investigating the correlation between the microbiota, BA and FXR have shown that conventionally raised (CONV-R) mice displayed a decrease in BA pool, in particular the reduction in T-MCA/CA ratio in the ileum, compared with germ free mice. The presence of gut microbiota in CONV-R mice upregulated FGF15 in the distal ileum through FXR-dependent pathway, however, it had no effect on the FXR activity in the liver. Generally, more profound microbial effects on BA composition were reported in the intestinal compartments with more abundant number of bacteria such as the cecum or colon [28]. A strong correlation between gut microbiome and BA composition was also demonstrated in mice treated with tempol, an antioxidant, which elevated BA level and reduced activity of bile salt hydrolases (BSH) [5], [14], [19]. BSHs are an important element in the BA homeostasis due to their ability to decompose BAs to other compounds used by intestinal bacteria [31]. It suppresses the synthesis of BAs de novo by affecting the expression of CYP7A1 [29]. BSH is produced by several strains of bacteria, such as Lactobacillus, Clostridium spp., Bifidobacterium, Enterococcus and Bacterioides[16], [4]. In the study, the administration of tempol to mice shifted bacterial environment from the phylum Firmicutes to Bacteroides which consequently decreased the production of short chain fatty acids [30], [32]. Tempol targets particularly secondary BAs conjugated to glycine, such as trichloroacetic, taurochenodeoxycholic, tauroursodeoxycholic acids which exert various affinity to FXR by up- or down-regulating its expression in the ileum; no alterations in the expression of FXR target genes were found in the liver [30], [32]. The obtained results show a strict correlation between FXR modulators (i.e. its agonists and antagonists), BAs and metabolites secreted by the gut microbiota.
Functional GI disorders IBS is a multifactorial disorder which course may fluctuate over time within the same patient. It is one of the most frequently diagnosed FGIDs with global prevalence reaching 11.2% [33]. Although the signs and symptoms of IBS vary from patient to patient, there are few relapsing manifestations that occur chronically, such as abdominal pain, discomfort associated with changes in bowel movement i.e. diarrhea or constipation, and bloating [34]. According to the Rome IV criteria, there are four types of IBS: constipation-predominant IBS (IBS-C), diarrhea-predominant IBS (IBS-D), IBS with mixed bowel habits and unclassified IBS [35]. IBS is recurrent in nature and has a negative impact on health-related quality of life of patients. The pathophysiology of the disease is not well understood but several factors can contribute to its development e.g. increased intestinal permeability, inappropriate diet and eating habits, altered intestinal microbiota or low-grade mucosal inflammation [33]. There is no specific treatment option thus IBS patients usually rely solely on the pharmacotherapy (e.g. probiotics, antibiotics, antidepressants, anticholinergics, antispasmodics, laxatives or prosecretory agents) and lifestyle modifications (e.g. dietary modifications, fiber administration) [36].