Abstract
Post-cholecystectomy diarrhea (PCD) is a common complication of gallbladder removal, and gut microbiota changes have been determined in PCD patients. Bile acid diarrhea (BAD) is supposed to be the main pathogenic factor for PCD due to the disrupted fecal bile acid metabolism in diarrheal patients. However, the profiling of bile acid metabolite alteration in PCD is unclear and whether changed gut microbiota and fecal bile acid metabolism are correlated is also underdetermined. The fecal bile acid metabolites from fecal samples were profiled by targeted UPLC/MS (ultra-high-performance liquid chromatography coupled with a triple-quadrupole mass spectrometer) and the composition of fecal bile acid metabolites in PCD patients was demonstrated to be distinct from those in Non-PCD and HC groups. In addition, the quantification of bile acid excretion in feces of diarrheal patients was significantly elevated. Furthermore, 16S rRNA sequencing results revealed that PCD patients had the lowest operational taxonomic units (OTU) and significant reduction in microbial richness and evenness. Bacterial composition was remarkably shifted in PCD patients, which mainly lay in dominated phyla Firmicutes and Bacteroidota. Besides, the co-abundance network among genus bacteria declined in PCD. Among the genera, Prevotella, Enterococcus, and Erysipelotrichaceae_UCG-003 were enriched, but Alistipes, Bacteroides, Ruminococcus, and Phascolarctobacterium were reduced. Moreover, these disease-linked genera were closely associated with several diarrheal phenotypes. Notably, changed bile acid metabolites exhibited strong correlations with gut microbiota as well. Conclusively, this study reveals associations between PCD-linked microbes and bile acid metabolites, which may synergistically correlate to postoperative diarrhea.
Highlights
Cholecystectomy remains the most common surgical procedure for symptomatic gallbladder diseases (Baron et al, 2015), and the mounting morbidity of cholelithiasis increases the performing frequency of this operation worldwide (Lammert et al, 2016)
post-cholecystectomy diarrhea (PCD) patients exhibited increased defecation output and frequency, and higher Bristol stool score (BSS), which met the diagnostic criteria for diarrhea (Table 1)
Microbial genome DNA were extracted from fecal samples and sequenced by 16S rRNA sequencing analysis and targeted metabolic profiling on fecal bile acids was performed on a subset of 20 samples (Figure 1A)
Summary
Cholecystectomy remains the most common surgical procedure for symptomatic gallbladder diseases (Baron et al, 2015), and the mounting morbidity of cholelithiasis increases the performing frequency of this operation worldwide (Lammert et al, 2016). It has been considered as a safe surgical approach for a long time and accumulating advances in minimally invasive surgery promote its clinical application (Baron et al, 2015). Profiling results of fecal bile acid metabolism in PCD patients are still unclear
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