Dataset Information

Fecal microbiome transplantation and tributyrin improves early cardiac dysfunction and modifies the BCAA metabolic pathway in a diet induced pre-HFpEF mouse model.

ABSTRACT: More than 50% of patients with heart failure present with heart failure with preserved ejection fraction (HFpEF), and 80% of them are overweight or obese. In this study we developed an obesity associated pre-HFpEF mouse model and showed an improvement in both systolic and diastolic early dysfunction following fecal microbiome transplant (FMT). Our study suggests that the gut microbiome-derived short-chain fatty acid butyrate plays a significant role in this improvement. Cardiac RNAseq analysis showed butyrate to significantly upregulate ppm1k gene that encodes protein phosphatase 2Cm (PP2Cm) which dephosphorylates and activates branched-chain α-keto acid dehydrogenase (BCKDH) enzyme, and in turn increases the catabolism of branched chain amino acids (BCAAs). Following both FMT and butyrate treatment, the level of inactive p-BCKDH in the heart was reduced. These findings show that gut microbiome modulation can alleviate early cardiac mechanics dysfunction seen in the development of obesity associated HFpEF.

SUBMITTER: Hatahet J

PROVIDER: S-EPMC9944585 | biostudies-literature | 2023

REPOSITORIES: biostudies-literature

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Fecal microbiome transplantation and tributyrin improves early cardiac dysfunction and modifies the BCAA metabolic pathway in a diet induced pre-HFpEF mouse model.

Hatahet Jomana J Cook Tyler M TM Bonomo Raiza R RR Elshareif Nadia N Gavini Chaitanya K CK White Chelsea R CR Jesse Jason J Mansuy-Aubert Virginie V Aubert Gregory G

Frontiers in cardiovascular medicine 20230208

More than 50% of patients with heart failure present with heart failure with preserved ejection fraction (HFpEF), and 80% of them are overweight or obese. In this study we developed an obesity associated pre-HFpEF mouse model and showed an improvement in both systolic and diastolic early dysfunction following fecal microbiome transplant (FMT). Our study suggests that the gut microbiome-derived short-chain fatty acid butyrate plays a significant role in this improvement. Cardiac RNAseq analysis s ...[more]

PMID: 36844730

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Project description:Butyrate and its derivatives possess various nutritional and biological benefits for mammals, whereas its effects on dairy calves have not been well characterized. This study evaluated the effects of tributyrin administration on blood immune, intestinal immune and barrier functions, and microbial composition of pre-weaned dairy calves. Twenty newborn Holstein bull calves were randomly assigned into a control group (no tributyrin supplementation, CON; n = 10) or a treatment group (supplemented with tributyrin at 2 g/L of milk, TRB; n = 10). The results showed that diarrhea frequency was decreased significantly by tributyrin administration from d 29 to 56 (P < 0.001) and the whole period (P = 0.003, d 1 to 56) though no significant effects were observed on growth performance. For blood metabolites, tributyrin administration significantly reduced the concentration of interleukin-1β (IL-1β) on d 28 (P = 0.001) and tended to reduce the concentration of serum amyloid A on d 56 (P = 0.079), whereas serum oxidative status parameters were not affected. For intestinal development, tributyrin administration increased the villus height (P < 0.001) and the ratio of villus height to crypt depth (P = 0.046) in the jejunum, and the villus height in the ileum (P = 0.074). Furthermore, toll-like receptor 2 (TRL2, P = 0.045) and IL-1β (P = 0.088) gene expressions were downregulated, while claudin-4 (P = 0.022) gene expression was upregulated in the jejunum following tributyrin administration. In the ileum, claudin-4 (P = 0.029) and G-protein coupled receptor 41 (P = 0.019) gene expressions were upregulated in the TRB group compared to CON. No significantly higher abundances of microbiota were found in the jejunum or ileum of calves in the CON group. In the TRB group, supplementing tributyrin significantly increased the abundance of short-chain fatty acid (SCFA)-producing bacteria, including Ruminococcaceae, Lachnospiraceae, Prevotella and Rikenellaceae (LDA >3.5, P < 0.05), which was negatively associated with inflammatory gene expression (TLR2 and IL-1β) but positively associated with intestinal barrier genes (claudin-4) and morphological parameters (P < 0.05). In conclusion, supplementing tributyrin in milk replacer could improve intestinal development and health of pre-weaned dairy calves by stimulating SCFA-producing bacteria colonization, enhancing intestinal barrier functions and suppressing inflammatory responses.

Project description:UnlabelledClostridium difficile infection is one of the most common health care-associated infections, and up to 40% of patients suffer from recurrence of disease following standard antibiotic therapy. Recently, fecal microbiota transplantation (FMT) has been successfully used to treat recurrent C. difficile infection. It is hypothesized that FMT aids in recovery of a microbiota capable of colonization resistance to C. difficile. However, it is not fully understood how this occurs. Here we investigated changes in the fecal microbiota structure following FMT in patients with recurrent C. difficile infection, and imputed a hypothetical functional profile based on the 16S rRNA profile using a predictive metagenomic tool. Increased relative abundance of Bacteroidetes and decreased abundance of Proteobacteria were observed following FMT. The fecal microbiota of recipients following transplantation was more diverse and more similar to the donor profile than the microbiota prior to transplantation. Additionally, we observed differences in the imputed metagenomic profile. In particular, amino acid transport systems were overrepresented in samples collected prior to transplantation. These results suggest that functional changes accompany microbial structural changes following this therapy. Further identification of the specific community members and functions that promote colonization resistance may aid in the development of improved treatment methods for C. difficile infection.ImportanceWithin the last decade, Clostridium difficile infection has surpassed other bacterial infections to become the leading cause of nosocomial infections. Antibiotic use, which disrupts the gut microbiota and its capability in providing colonization resistance against C. difficile, is a known risk factor in C. difficile infection. In particular, recurrent C. difficile remains difficult to treat with standard antibiotic therapy. Fecal microbiota transplantation (FMT) has provided a successful treatment method for some patients with recurrent C. difficile infection, but its mechanism and long-term effects remain unknown. Our results provide insight into the structural and potential metabolic changes that occur following FMT, which may aid in the development of new treatment methods for C. difficile infection.

Project description:Opportunistic feeding and multiple other environment factors can modulate the gut microbiome, and bias conclusions, when wild animals are used for studying the influence of phylogeny and diet on their gut microbiomes. Here, we controlled for these other confounding factors in our investigation of the magnitude of the effect of diet on the gut microbiome assemblies of nonpasserine birds. We collected fecal samples, at one point in time, from 35 species of birds in a single zoo as well as 6 species of domestic poultry from farms in Guangzhou city to minimize the influences from interfering factors. Specifically, we describe 16S rRNA amplicon data from 129 fecal samples obtained from 41 species of birds, with additional shotgun metagenomic sequencing data generated from 16 of these individuals. Our data show that diets containing native starch increase the abundance of Lactobacillus in the gut microbiome, while those containing plant-derived fiber mainly enrich the level of Clostridium Greater numbers of Fusobacteria and Proteobacteria are detected in carnivorous birds, while in birds fed a commercial corn-soybean basal diet, a stronger inner-connected microbial community containing Clostridia and Bacteroidia was enriched. Furthermore, the metagenome functions of the microbes (such as lipid metabolism and amino acid synthesis) were adapted to the different food types to achieve a beneficial state for the host. In conclusion, the covariation of diet and gut microbiome identified in our study demonstrates a modulation of the gut microbiome by dietary diversity and helps us better understand how birds live based on diet-microbiome-host interactions.IMPORTANCE Our study identified food source, rather than host phylogeny, as the main factor modulating the gut microbiome diversity of nonpasserine birds, after minimizing the effects of other complex interfering factors such as weather, season, and geography. Adaptive evolution of microbes to food types formed a dietary-microbiome-host interaction reciprocal state. The covariation of diet and gut microbiome, including the response of microbiota assembly to diet in structure and function, is important for health and nutrition in animals. Our findings help resolve the major modulators of gut microbiome diversity in nonpasserine birds, which had not previously been well studied. The diet-microbe interactions and cooccurrence patterns identified in our study may be of special interest for future health assessment and conservation in birds.

Dataset Information

Fecal microbiome transplantation and tributyrin improves early cardiac dysfunction and modifies the BCAA metabolic pathway in a diet induced pre-HFpEF mouse model.

Publications

Fecal microbiome transplantation and tributyrin improves early cardiac dysfunction and modifies the BCAA metabolic pathway in a diet induced pre-HFpEF mouse model.

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