Lactobacillus delbrueckii Ameliorated Blood Lipids via Intestinal Microbiota Modulation and Fecal Bile Acid Excretion in a Ningxiang Pig Model
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ABSTRACT:
SUBMITTER: Hou G
PROVIDER: S-EPMC11201289 | biostudies-literature | 2024 Jun
REPOSITORIES: biostudies-literature
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Project description:BackgroundGut microbiota has been extensively demonstrated to modulate host lipid metabolism. Higher intramuscular fat (IMF) accumulation in Chinese indigenous breed pigs is associated with their special gut microbiota structure. However, the specific microbes and metabolic pathways responsible for lipid deposition are still poorly understood.ResultsIn the present study, a comparative analysis of the gut microbiota and metabolome in obese Ningxiang (NX) pigs and lean Duroc × Landrace × Yorkshire (DLY) pigs was conducted. The results revealed a higher abundance of gut lactobacilli and a correlation of branched-chain amino acid (BCAA) metabolism pathway in NX pigs. We proceeded to verify the roles of various lactobacilli strains originating from NX pigs in BCAA metabolism and lipids deposition in SD rats. We demonstrated that L. reuteri is a fundamental species responsible for modulating lipid deposition in NX pigs and that increased circulating levels of BCAA are positively linked to greater lipid deposition. Additionally, it has been verified that L. reuteri originating from NX pigs has the ability to improve BCAA synthesis in the gut and enhance IMF content in lean DLY pigs. The expression of genes related to lipid synthesis was also significantly upregulated.ConclusionsTaken together, our results imply that NX pig-derived L. reuteri regulates BCAA metabolism and plays a potential role in improving the meat quality of lean pig breeds through modulation of host intramuscular lipid deposition. The results provide a new strategy for improving the meat quality of commercial pigs by influencing host metabolism through supplementing dietary additives. Video Abstract.
| S-EPMC11786426 | biostudies-literature
Project description:Gut microbiota dysbiosis is involved in cholestatic liver diseases. However, the mechanisms remain to be elucidated. The purpose of this study was to examine the effects and mechanisms of Lactobacillus acidophilus (L. acidophilus) on cholestatic liver injury in both animals and humans. Bile duct ligation (BDL) was performed to mimic cholestatic liver injury in mice and serum liver function was tested. Gut microbiota were analyzed by 16S rRNA sequencing. Fecal bacteria transplantation (FMT) was used to evaluate the role of gut microbiota in cholestasis. Bile acids (BAs) profiles were analyzed by targeted metabolomics. Effects of L. acidophilus in cholestatic patients were evaluated by a randomized controlled clinical trial (NO: ChiCTR2200063330). BDL induced different severity of liver injury, which was associated with gut microbiota. 16S rRNA sequencing of feces confirmed the gut flora differences between groups, of which L. acidophilus was the most distinguished genus. Administration of L. acidophilus after BDL significantly attenuated hepatic injury in mice, decreased liver total BAs and increased fecal total BAs. Furthermore, after L. acidophilus treatment, inhibition of hepatic Cholesterol 7α-hydroxylase (CYP7α1), restored ileum Fibroblast growth factor 15 (FGF15) and Small heterodimer partner (SHP) accounted for BAs synthesis decrease, whereas enhanced BAs excretion was attributed to the increase of unconjugated BAs by enriched bile salt hydrolase (BSH) enzymes in feces. Similarly, in cholestasis patients, supplementation of L. acidophilus promoted the recovery of liver function and negatively correlated with liver function indicators, possibly in relationship with the changes in BAs profiles and gut microbiota composition. L. acidophilus treatment ameliorates cholestatic liver injury through inhibited hepatic BAs synthesis and enhances fecal BAs excretion.
| S-EPMC11364073 | biostudies-literature
Project description:Few studies have investigated the peptidomics of fermented milk by Lactobacillus delbrueckii. The aim of the present study was to interpret the peptidomic pattern of the fermented milk by five strains of L. delbrueckii ssp. bulgaricus and ssp. lactis prior to and after the simulated gastrointestinal digestion in vitro. The results indicated variations in the peptidomics among the samples, particularly between the samples of different subspecies. The peptides originating from β-casein were abundant in the samples of ssp. bulgaricus, whereas the peptides derived from αs1-casein and αs2-casein were more likely to dominate in those of ssp. lactis. For β-casein, the strains of ssp. bulgaricus displayed extensive hydrolysis in the regions of (73-97), (100-120), and (130-209), whereas ssp. lactis mainly focused on (160-209). The digestion appears to reduce the variations of the peptidomics profile in general. Among the five strains, L. delbrueckii ssp. bulgaricus DQHXNS8L6 was the most efficient in the generation of bioactive peptides prior to and after digestion. This research provided an approach for evaluating the peptide profile of the strains during fermentation and digestion.
| S-EPMC8701751 | biostudies-literature
Project description:ObjectivesApproximately 25% of patients with irritable bowel syndrome-diarrhea (IBS-D) have increased total fecal bile acids (BA) and serum C4 (surrogate for BA synthesis). BA synthesis-related genes (KLB and FGFR4) are associated with colonic transit (CT) in IBS-D. Our aims were: (i) to compare phenotype and pathophysiology in IBS-D patients with increased or normal fecal excretion or synthesis of BA; and (ii) to explore association of variations in two candidate bile-acid synthesis genes (KLB and FGFR4) in these two subgroups of IBS-D.MethodsA total of 64 IBS-D patients underwent on one occasion: fasting serum C4 and FGF19, total fecal fat and BA excretion, CT, intestinal and colonic permeability, and candidate genotyping (rs17618244 (KLB), rs351855 (FGFR4)). Colonic sensation and tone were measured in 47 of the IBS-D patients. IBS-D subgroups were identified by fecal BA >2,337 mM per 48 h or by serum C4 >47.1 ng/ml.ResultsIBS-D patients with fecal BA >2,337 mM per 48 h (19/54) had significantly greater body mass index, fecal fat, percent chenodeoxycholic acid (CDCA) in feces, and intestinal permeability, and borderline increased CT (P=0.13). Those IBS-D patients with serum C4 >47.1 ng/ml (13/54) had increased total fecal BA excretion and borderline increased colonic permeability. Variants in genes involved in feedback regulation of BA synthesis (KLB, P=0.06 and FGFR4, P=0.09) were potentially associated with the subgroup with elevated serum C4.ConclusionsIBS-D with increased BA excretion or synthesis is associated with significant pathophysiological changes relative to patients with normal BA profile. BA diarrhea is identified more effectively with total fecal BA than with serum C4.
| S-EPMC6994231 | biostudies-literature
Project description:Microbiota-targeted therapies for hypercholesterolemia get more and more attention and are recognized as an effective strategy for preventing and treating cardiovascular disease. The experiment was conducted to investigate the cholesterol-lowering mechanism of Lactobacillus delbrueckii in a pig model. Twelve barrows (38.70 ± 5.33 kg) were randomly allocated to two groups and fed corn-soybean meal diets with either 0% (Con) or 0.1% Lactobacillus delbrueckii (Con + LD) for 28 days. L. delbrueckii-fed pigs had lower serum contents of total cholesterol (TC), total bile acids (TBAs), and triglyceride, but higher fecal TC and TBA excretion. L. delbrueckii treatment increased ileal Lactobacillus abundance and bile acid (BA) deconjugation and affected serum and hepatic BA composition. Dietary L. delbrueckii downregulated the gene expression of ileal apical sodium-dependent bile acid transporter (ASBT) and ileal bile acid binding protein (IBABP), and hepatic farnesoid X receptor (FXR), fibroblast growth factor (FGF19), and small heterodimer partner (SHP), but upregulated hepatic high-density lipoprotein receptor (HDLR), low-density lipoprotein receptor (LDLR), sterol regulatory element binding protein-2 (SREBP-2), and cholesterol-7α hydroxylase (CYP7A1) expression. Our results provided in vivo evidence that L. delbrueckii promote ileal BA deconjugation with subsequent fecal TC and TBA extraction by modifying ileal microbiota composition and induce hepatic BA neosynthesis via regulating gut-liver FXR-FGF19 axis.
| S-EPMC7759492 | biostudies-literature
Project description:Background and aimsCholestatic liver disease is characterized by gut dysbiosis and excessive toxic hepatic bile acids (BAs). Modification of gut microbiota and repression of BA synthesis are potential strategies for the treatment of cholestatic liver disease. The purpose of this study was to examine the effects and to understand the mechanisms of the probiotic Lactobacillus rhamnosus GG (LGG) on hepatic BA synthesis, liver injury, and fibrosis in bile duct ligation (BDL) and multidrug resistance protein 2 knockout (Mdr2-/- ) mice.Approach and resultsGlobal and intestine-specific farnesoid X receptor (FXR) inhibitors were used to dissect the role of FXR. LGG treatment significantly attenuated liver inflammation, injury, and fibrosis with a significant reduction of hepatic BAs in BDL mice. Hepatic concentration of taurine-β-muricholic acid (T-βMCA), an FXR antagonist, was markedly increased in BDL mice and reduced in LGG-treated mice, while chenodeoxycholic acid, an FXR agonist, was decreased in BDL mice and normalized in LGG-treated mice. LGG treatment significantly increased the expression of serum and ileum fibroblast growth factor 15 (FGF-15) and subsequently reduced hepatic cholesterol 7α-hydroxylase and BA synthesis in BDL and Mdr2-/- mice. At the molecular level, these changes were reversed by global and intestine-specific FXR inhibitors in BDL mice. In addition, LGG treatment altered gut microbiota, which was associated with increased BA deconjugation and increased fecal and urine BA excretion in both BDL and Mdr2-/- mice. In vitro studies showed that LGG suppressed the inhibitory effect of T-βMCA on FXR and FGF-19 expression in Caco-2 cells.ConclusionLGG supplementation decreases hepatic BA by increasing intestinal FXR-FGF-15 signaling pathway-mediated suppression of BA de novo synthesis and enhances BA excretion, which prevents excessive BA-induced liver injury and fibrosis in mice.
| S-EPMC7317518 | biostudies-literature
Project description:Sixteen 35-day-old piglets, including eight Large White (LW) piglets (a lean-type pig breed) and eight Ningxiang (NX) piglets (a fatty-type Chinese Indigenous pig breed), were fed the same diet for 105 days. NX pigs had higher intramuscular fat content than LW pigs (p < 0.05). According to 16S rRNA gene sequencing, the relative abundances of the genera Ruminococcaceae_NK4A214_group, Parabacteroides, Christensenellaaceae_R-7_group and Ruminiclostridium were higher, whereas the abundances of Prevotellaceae_NK3B31_group, Prevotella, Subdoligranulum and Faecalibacterium were lower, in the colon of NX pigs compared to that of LW pigs. Nonmetric multidimensional scaling analysis revealed that the microbiota of the two pig breeds clustered separately along the principal coordinate axis. Furthermore, functional prediction of the bacterial communities suggested higher fatty acid biosynthesis in NX pigs. NX pigs also exhibited lower concentrations of total short-chain fatty acids, propionate and butyrate in the colon (p < 0.05). These findings suggest that NX pigs exhibited higher intramuscular fat content and backfat thickness than LW pigs. The bacterial communities in the colon of NX pigs were also more diverse than those in the colon of LW pigs, which might be used as a potential metabolomics mechanism to research different breeds of pigs.
| S-EPMC8300102 | biostudies-literature
Project description:Bile acid sequestrants (BASs) are cholesterol-lowering drugs that also affect hyperglycemia. The mechanism by which BASs exert these and other metabolic effects beyond cholesterol lowering remains poorly understood. The present study aimed to investigate the effects of a BAS, colestilan, on body weight, energy expenditure, and glucose and lipid metabolism and its mechanisms of action in high-fat-fed hyperlipidemic APOE*3 Leiden (E3L) transgenic mice. Mildly insulin-resistant E3L mice were fed a high-fat diet with or without 1.5% colestilan for 8 weeks. Colestilan treatment decreased body weight, visceral and subcutaneous fat, and plasma cholesterol and triglyceride levels but increased food intake. Blood glucose and plasma insulin levels were decreased, and hyperinsulinemic-euglycemic clamp analysis demonstrated improved insulin sensitivity, particularly in peripheral tissues. In addition, colestilan decreased energy expenditure and physical activity, whereas it increased the respiratory exchange ratio, indicating that colestilan induced carbohydrate catabolism. Moreover, kinetic analysis revealed that colestilan increased [(3)H]NEFA incorporation in biliary cholesterol and phospholipids and increased fecal lipid excretion. Gene expression analysis in liver, fat, and muscle supported the above findings. In summary, colestilan decreases weight gain and improves peripheral insulin sensitivity in high-fat-fed E3L mice by enhanced NEFA incorporation in biliary lipids and increased fecal lipid excretion.
| S-EPMC3622322 | biostudies-literature
Project description:Lactobacillus delbrueckii comprises six subspecies, L. delbrueckii subsp. bulgaricus, L. delbrueckii subsp. lactis, L. delbrueckii subsp. jakobsenii, L. delbrueckii subsp. delbrueckii, L. delbrueckii subsp. sunkii, and L. delbrueckii subsp. indicus. We investigated the evolution of the six subspecies of L. delbrueckii using comparative genomics. While the defining feature of the species was the gene number increment driven by mobile elements and gene fragmentation, the repertoire of subspecies-specific gene gains and losses differed among the six subspecies. The horizontal gene transfer analyses indicated that frequent gene transfers between different subspecies had occurred when the six subspecies first diverged from the common ancestor, but recent gene exchange was confined to a subspecies implying independent evolution of the six subspecies. The subspecies bulgaricus is a homogeneous group that diverged from the other subspecies a long time ago and underwent convergent evolution. The subspecies lactis, jakobsenii, delbrueckii, and sunkii were more closely related to each other than to other subspecies. The four subspecies commonly show increasing genetic variability with increasing genome size. However, the four subspecies were distinguished by specific gene contents. The subspecies indicus forms a branch distant from the other subspecies and shows an independent evolutionary trend. These results could explain the differences in the habitat and nutritional requirements of the subspecies of L. delbrueckii.
| S-EPMC9950072 | biostudies-literature
Project description:BackgroundDihydromyricetin (DMY) is a natural flavonoid with anti-nonalcoholic steatohepatitis (NASH) activity. However, the effects of DMY on the composition of lipids and bile acids (BAs) in serum, and gut microbiota (GM) in ileum of mice with NASH are not clear.MethodsAfter male C57BL/6 mice was fed with methionine and choline deficiency (MCD) diet and simultaneously administered with DMY (300 mg/kg/day) by gavage for 8 weeks, the pathological changes of liver tissue were observed by Oil Red O, hematoxylin eosin and Masson staining, the levels of serum alaninea minotransferase, aspartate aminotransferase and liver triglyceride, malonic dialdehyde were detected by the detection kits, the composition and contents of serum lipids and BAs were detected by Liquid Chromatograph-Mass Spectrometry, the mRNA levels of hepatic BAs homeostasis-related genes were detected by RT-qPCR, and microbiological diversity in ileum was analyzed by 16S rDNA sequencing.ResultsThe results showed that the significant changes including 29 lipids, 4 BAs (23-nor-deoxycholic acid, ursodeoxycholic acid, 7-ketodeoxycholic acid and cholic acid), 2 BA transporters (Mrp2 and Oatp1b2) and 8 GMs between MCD and DMY groups. Among them, DMY treatment significantly down-regulated 21 lipids, 4 BAs mentioned above, the ratio of Firmicutes/Bacteroidota and the abundance of Erysipelotrichaceae, Faecalibacuium, significantly up-regulated 8 lipids and 5 GMs (Verrucomicrobiota, Bacteroidota, Actinobacteria, Akkermansiaceae and Akkermansia).ConclusionsThe results suggested that DMY may alleviate MCD diet-induced NASH through decreasing the serum levels of toxic BAs which regulated by liver Oatp1b2 and Mrp2, regulating the metabolism of related lipids, and up-regulating intestinal probiotics (Actinobacteria and Verrucomicrobiota at the phylum level; Akkermansiaceae at the family level; Akkermansiaat at the genus level) and inhibiting intestinal harmful bacteria (Firmicutes at the phylum level; Erysipelotrichaceae at the family level; Faecalibaculum at the genus level).
| S-EPMC10394885 | biostudies-literature