Antimicrobial promotion of pig growth is associated with tissue-specific remodeling of bile acid signature and signaling

Ipharraguerre, I.R.; Pastor, Jose J.; Gavaldà‐Navarro, Aleix; Villarroya, Francesc; Mereu, Alessandro

doi:10.1038/s41598-018-32107-9

Cited by 14 publications

(22 citation statements)

References 70 publications

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“…Our study clarified a causal relationship between Clostridia bacteria and intestinal FGF19 deficiency. Antimicrobial studies in piglets showing that amoxicillin decreased abundances of Clostridium bacteria but enhanced animal ileal and serum FGF19 levels (56) also support such a relationship. Given that there is intestinal crosstalk between gut bacteria and BAs (22), we cannot exclude the possibility that enrichment of Clostridia bacteria might be secondary to the BA abnormality induced by FGF19 deficiency.…”

Section: Discussionmentioning

confidence: 92%

A Clostridia-rich microbiota enhances bile acid excretion in diarrhea-predominant irritable bowel syndrome

Zhao

Yang

Chen

et al. 2019

Journal of Clinical Investigation

135

114

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An excess of fecal bile acids (BAs) is thought to be one of the mechanisms for diarrhea-predominant irritable bowel syndrome (IBS-D). However, the factors causing excessive BA excretion remain incompletely studied. Given the importance of gut microbiota in BA metabolism, we hypothesized that gut dysbiosis might contribute to excessive BA excretion in IBS-D. By performing BA-related metabolic and metagenomic analyses in 290 IBS-D patients and 89 healthy volunteers, we found that 24.5% of IBS-D patients exhibited excessive excretion of total BAs and alteration of BA-transforming bacteria in feces. Notably, the increase in Clostridia bacteria (e.g., C. scindens) was positively associated with the levels of fecal BAs and serum 7α-hydroxy-4-cholesten-3-one (C4), but negatively correlated with serum fibroblast growth factor 19 (FGF19) concentration. Furthermore, colonization with Clostridia-rich IBS-D fecal microbiota or C. scindens individually enhanced serum C4 and hepatic conjugated BAs but reduced ileal FGF19 expression in mice. Inhibition of Clostridium species with vancomycin yielded opposite results. Clostridia-derived BAs suppressed the intestinal FGF19 expression in vitro and in vivo. In conclusion, this study demonstrates that the Clostridia-rich microbiota contributes to excessive BA excretion in IBS-D patients, which provides a mechanistic hypothesis with testable clinical implications.

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Section: Discussionmentioning

confidence: 92%

A Clostridia-rich microbiota enhances bile acid excretion in diarrhea-predominant irritable bowel syndrome

Zhao

Yang

Chen

et al. 2019

Journal of Clinical Investigation

135

114

View full text Add to dashboard Cite

show abstract

“…The hypocholesterolemic effect of probiotics is due in part to their BA deconjugating activity, which reduces cholesterol solubility and absorption in the gut, and increases cholesterol utilization in the liver to replace secondary BAs lost in feces (57). In this regard, probiotics decreased microbial diversity in the hindgut, and increased weight gain in the CON-P group, effects which have been connected to increased secondary BA production in antimicrobial-treated pigs (48). However, probiotic supplementation did not change colonic BA levels or BSH active genera compared with nonprobiotic groups, and increased both liver weight and hepatocellular degeneration in HFF-fed pigs.…”

Section: Discussionmentioning

confidence: 99%

Dysregulated FXR-FGF19 signaling and choline metabolism are associated with gut dysbiosis and hyperplasia in a novel pig model of pediatric NASH

Hernandez

Smith

Melnyk

et al. 2020

American Journal of Physiology-Gastrointestinal and Liver Physi

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To investigate the role of bile acids (BAs) in the pathogenesis of diet-induced nonalcoholic steatohepatitis (NASH), we fed a “Western-style diet” [high fructose, high fat (HFF)] enriched with fructose, cholesterol, and saturated fat for 10 wk to juvenile Iberian pigs. We also supplemented probiotics with in vitro BA deconjugating activity to evaluate their potential therapeutic effect in NASH. Liver lipid and function, cytokines, and hormones were analyzed using commercially available kits. Metabolites, BAs, and fatty acids were measured by liquid chromatography-mass spectrometry. Histology and gene and protein expression analyses were performed using standard protocols. HFF-fed pigs developed NASH, cholestasis, and impaired enterohepatic Farnesoid-X receptor (FXR)-fibroblast growth factor 19 (FGF19) signaling in the absence of obesity and insulin resistance. Choline depletion in HFF livers was associated with decreased lipoprotein and cholesterol in serum and an increase of choline-containing phospholipids in colon contents and trimethylamine- N-oxide in the liver. Additionally, gut dysbiosis and hyperplasia increased with the severity of NASH, and were correlated with increased colonic levels of choline metabolites and secondary BAs. Supplementation of probiotics in the HFF diet enhanced NASH, inhibited hepatic autophagy, increased excretion of taurine and choline, and decreased gut microbial diversity. In conclusion, dysregulation of BA homeostasis was associated with injury and choline depletion in the liver, as well as increased biliary secretion, gut metabolism and excretion of choline-based phospholipids. Choline depletion limited lipoprotein synthesis, resulting in hepatic steatosis, whereas secondary BAs and choline-containing phospholipids in colon may have promoted dysbiosis, hyperplasia, and trimethylamine synthesis, causing further damage to the liver. NEW & NOTEWORTHY Impaired Farnesoid-X receptor (FXR)-fibroblast growth factor 19 (FGF19) signaling and cholestasis has been described in nonalcoholic fatty liver disease (NAFLD) patients. However, therapeutic interventions with FXR agonists have produced contradictory results. In a swine model of pediatric nonalcoholic steatohepatitis (NASH), we show that the uncoupling of intestinal FXR-FGF19 signaling and a decrease in FGF19 levels are associated with a choline-deficient phenotype of NASH and increased choline excretion in the gut, with the subsequent dysbiosis, colonic hyperplasia, and accumulation of trimethylamine- N-oxide in the liver.

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“…Indeed, mice abundant in muricholic BAs showed resistance to diet-induced weight gain ( Bonde et al, 2016 ). Likewise, the antimicrobial promotion of pig growth has been shown to be associated with the remodeling of the BA signature in the intestine ( Ipharraguerre et al, 2018 ).…”

Section: Introductionmentioning

confidence: 99%

Reduced Feeding Frequency Improves Feed Efficiency Associated With Altered Fecal Microbiota and Bile Acid Composition in Pigs

Yan

Wei

et al. 2021

Front. Microbiol.

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A biphasic feeding regimen exerts an improvement effect on feed efficiency of pigs. While gut microbiome and metabolome are known to affect the host phenotype, so far the effects of reduced feeding frequency on fecal microbiota and their metabolism in pigs remain unclear. Here, the combination of 16S rRNA sequencing technique as well as untargeted and targeted metabolome analyses was adopted to investigate the fecal microbiome and metabolome of growing–finishing pigs in response to a biphasic feeding [two meals per day (M2)] pattern. Sixty crossbred barrows were randomly assigned into two groups with 10 replicates (three pigs/pen), namely, the free-access feeding group (FA) and the M2 group. Pigs in the FA group were fed free access while those in the M2 group were fed ad libitum twice daily for 1 h at 8:00 and 18:00. Results showed that pigs fed biphasically exhibited increased feed efficiency compared to FA pigs. The Shannon and Simpson indexes were significantly increased by reducing the feeding frequency. In the biphasic-fed pigs, the relative abundances of Subdoligranulum, Roseburia, Mitsuokella, and Terrisporobacter were significantly increased while the relative abundances of unidentified_Spirochaetaceae, Methanobrevibacter, unidentified_Bacteroidales, Alloprevotella, Parabacteroides, and Bacteroides were significantly decreased compared to FA pigs. Partial least-square discriminant analysis (PLS-DA) analysis revealed an obvious variation between the FA and M2 groups; the differential features were mainly involved in arginine, proline, glycine, serine, threonine, and tryptophan metabolism as well as primary bile acid (BA) biosynthesis. In addition, the changes in the microbial genera were correlated with the differential fecal metabolites. A biphasic feeding regimen significantly increased the abundances of primary BAs and secondary BAs in feces of pigs, and the differentially enriched BAs were positively correlated with some specific genera. Taken together, these results suggest that the improvement effect of a reduced feeding frequency on feed efficiency of pigs might be associated with the altered fecal microbial composition and fecal metabolite profile in particular the enlarged stool BA pool.

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Antimicrobial promotion of pig growth is associated with tissue-specific remodeling of bile acid signature and signaling

Cited by 14 publications

References 70 publications

A Clostridia-rich microbiota enhances bile acid excretion in diarrhea-predominant irritable bowel syndrome

A Clostridia-rich microbiota enhances bile acid excretion in diarrhea-predominant irritable bowel syndrome

Dysregulated FXR-FGF19 signaling and choline metabolism are associated with gut dysbiosis and hyperplasia in a novel pig model of pediatric NASH

Reduced Feeding Frequency Improves Feed Efficiency Associated With Altered Fecal Microbiota and Bile Acid Composition in Pigs

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