Dataset Information

Correlation between Peptacetobacter hiranonis, the baiCD Gene, and Secondary Bile Acids in Dogs.

ABSTRACT: Bile acid metabolism is a key pathway modulated by intestinal microbiota. Peptacetobacter (Clostridium) hiranonis has been described as the main species responsible for the conversion of primary into secondary fecal unconjugated bile acids (fUBA) in dogs. This multi-step biochemical pathway is encoded by the bile acid-inducible (bai) operon. We aimed to assess the correlation between P. hiranonis abundance, the abundance of one specific gene of the bai operon (baiCD), and secondary fUBA concentrations. In this retrospective study, 133 fecal samples were analyzed from 24 dogs. The abundances of P. hiranonis and baiCD were determined using qPCR. The concentration of fUBA was measured by gas chromatography-mass spectrometry. The baiCD abundance exhibited a strong positive correlation with secondary fUBA (ρ = 0.7377, 95% CI (0.6461, 0.8084), p < 0.0001). Similarly, there was a strong correlation between P. hiranonis and secondary fUBA (ρ = 0.6658, 95% CI (0.5555, 0.7532), p < 0.0001). Animals displaying conversion of fUBA and lacking P. hiranonis were not observed. These results suggest P. hiranonis is the main converter of primary to secondary bile acids in dogs.

SUBMITTER: Correa Lopes B

PROVIDER: S-EPMC10812727 | biostudies-literature | 2024 Jan

REPOSITORIES: biostudies-literature

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Correlation between Peptacetobacter hiranonis, the baiCD Gene, and Secondary Bile Acids in Dogs.

Correa Lopes Bruna B Chen Chih-Chun CC Sung Chi-Hsuan CH Ishii Patricia Eri PE Medina Luis Fernando da Costa LFDC Gaschen Frederic P FP Suchodolski Jan S JS Pilla Rachel R

Animals : an open access journal from MDPI 20240109 2

Bile acid metabolism is a key pathway modulated by intestinal microbiota. Peptacetobacter (Clostridium) hiranonis has been described as the main species responsible for the conversion of primary into secondary fecal unconjugated bile acids (fUBA) in dogs. This multi-step biochemical pathway is encoded by the bile acid-inducible (bai) operon. We aimed to assess the correlation between P. hiranonis abundance, the abundance of one specific gene of the bai o ...[more]

PMID: 38254385

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Project description:BackgroundSignificantly elevated serum and hepatic bile acid (BA) concentrations have been known to occur in patients with liver fibrosis. However, the roles of different BA species in liver fibrogenesis are not fully understood.MethodsWe quantitatively measured blood BA concentrations in nonalcoholic steatohepatitis (NASH) patients with liver fibrosis and healthy controls. We characterized BA composition in three mouse models induced by carbon tetrachloride (CCl4), streptozotocin-high fat diet (STZ-HFD), and long term HFD, respectively. The molecular mechanisms underlying the fibrosis-promoting effects of BAs were investigated in cell line models, a 3D co-culture system, and a Tgr5 (HSC-specific) KO mouse model.FindingsWe found that a group of conjugated 12α-hydroxylated (12α-OH) BAs, such as taurodeoxycholate (TDCA) and glycodeoxycholate (GDCA), significantly increased in NASH patients and liver fibrosis mouse models. 12α-OH BAs significantly increased HSC proliferation and protein expression of fibrosis-related markers. Administration of TDCA and GDCA directly activated HSCs and promoted liver fibrogenesis in mouse models. Blockade of BA binding to TGR5 or inhibition of ERK1/2 and p38 MAPK signaling both significantly attenuated the BA-induced fibrogenesis. Liver fibrosis was attenuated in mice with Tgr5 depletion.InterpretationIncreased hepatic concentrations of conjugated 12α-OH BAs significantly contributed to liver fibrosis via TGR5 mediated p38MAPK and ERK1/2 signaling. Strategies to antagonize TGR5 or inhibit ERK1/2 and p38 MAPK signaling may effectively prevent or reverse liver fibrosis.FundingsThis study was supported by the National Institutes of Health/National Cancer Institute Grant 1U01CA188387-01A1, the National Key Research and Development Program of China (2017YFC0906800); the State Key Program of National Natural Science Foundation (81430062); the National Natural Science Foundation of China (81974073, 81774196), China Postdoctoral Science Foundation funded project, China (2016T90381), and E-institutes of Shanghai Municipal Education Commission, China (E03008).

Project description:The aim of this study was to investigate the reasons for the differences in lipid accumulation between lean and obese pigs. The bile acids with varying levels within two types of pigs were found and then in vitro experiments were conducted to identify whether these bile acids can directly affect lipid accumulation. Fourteen pigs, including seven lean and seven obese pigs with body weights of approximately 80 kg, were fed the same diet at an amount approximately equivalent to 3% of their respective body weights daily for 42 d. In vitro, 3T3-L1 preadipocytes were cultured in medium with high glucose levels and were differentiated into mature adipocytes using differentiation medium. Then, bile acids were added to mature adipocytes for 4 d. The results showed that there was a difference in body lipids levels and gut microbiota composition between obese and lean pigs (P < 0.05). According to the results of gut microbial function prediction, the bile acid biosynthesis in colonic digesta of obese pigs were different from that in lean pig. Sixty-five bile acids were further screened by metabolomics, of which 4 were upregulated (P < 0.05) and 2 were downregulated (P < 0.05) in obese pigs compared to lean pigs. The results of the correlation analysis demonstrated that chenodeoxycholic acid-3-β-D-glucuronide (CDCA-3Gln) and ω-muricholic acid (ω-MCA) had a negative correlation with abdominal fat weight and abdominal fat rate, while isoallolithocholic acid (IALCA) was positively associated with crude fat in the liver and abdominal fat rate. There was a positive correlation between loin muscle area and CDCA-3Gln and ω-MCA (P < 0.05), however, IALCA and 3-oxodeoxycholic acid (3-oxo-DCA) were negatively associated with loin eye muscle area (P < 0.05). Isoallolithocholic acid increased the gene expression of peroxisome proliferator-activated receptor gamma (PPARG) and the number of lipid droplets (P < 0.05), promoting the lipid storage when IALCA was added to 3T3-L1 mature adipocytes in vitro. In conclusion, the concentration of bile acids, especially gut microbiota related-secondary bile acids, in obese pigs was different from that in lean pigs, which may contribute to lipid accumulation within obese pigs.

Dataset Information

Correlation between Peptacetobacter hiranonis, the baiCD Gene, and Secondary Bile Acids in Dogs.

Publications

Correlation between <i>Peptacetobacter hiranonis</i>, the <i>baiCD</i> Gene, and Secondary Bile Acids in Dogs.

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