Biology subjects

Vital, M.

Publications and source records attributed to Vital, M..

4 recordsLinked to original sources

bioRxiv2025

A potential role of altered SIgA-targeting of gut microbiota in long-term dysbiosis in pediatric solid organ transplant recipients

BackgroundComposition of gut microbiota (GM) is altered in solid organ transplantation (SOT) patients, where the degree of dysbiosis is associated with long-term survival. Factors governing dysbiosis are poorly understood with immunosuppression therapy believed to be involved in altering GM composition in those patients, either directly or via the immune system. At the interface stands secretory (S)IgA, however, little is known on its role governing dysbiosis in the context of SOT. In this study, we performed quantitative metagenomic analyses of GM accompanied by SIgA sequencing in 48 pediatric SOT recipients (age = 10.6 {+/-} 4.7 years) receiving either a heart (HTR, n=10), a kidney (KTR, n=11) or a liver (LTR, n=27) and compared results to healthy controls (HC, n=16). ResultsWe confirmed compositional and functional dysbiosis in SOT patients that broadly clustered into two groups, where cluster 1 (n=23) comprised most LTR patients and was closer to HC compared with cluster 2 (n=24) that exhibited stronger dysbiosis and included most HTR and KTR patients. The degree of dysbiosis was associated with Tacrolimus (TAC) levels. Overall, patients exhibited higher SIgA levels than HC, along with an increased percentage of bacteria targeted and altered target spectra. Furthermore, altered SIgA responses were associated with the degree of dysbiosis and were especially increased in cluster 2, in particular in HTR patients. A mechanistic model connecting immunosuppression, GM composition and SIgA targeting is proposed. ConclusionOur study suggests that altered SIgA responses play an important role for GM alterations observed in SOT patients. It opens new therapeutic angles to combat GM dysbiosis and associated long-erm complications.

microbiology↗

bioRxiv2025

Composition and short chain fatty acid formation of pig fecal microbiota during growth on predigested wheat and rye in vitro

BackgroundWhile wheat is the most commonly used cereal in pig feeding, rye has gained renewed interest as a component in pig diets due to its positive effects on gut health. The effects of distinct cereal sources on the composition and functionality of gut microbiota are, however, poorly investigated so far. In vitro studies offer a valuable approach to gain detailed insights on this matter, however, require a substrate that closely mimics the conditions found in the large intestine. In this study, we performed predigestion of cereal substrates using ileo-cecally fistulated minipigs simulating the upper gastrointestinal digestion. The composition of microbiota, total cell counts, and short chain fatty acid concentrations after a 24-hour incubation were analysed. Results were compared to cultures containing native substrates. ResultsBoth acetate and propionate concentration were significantly higher in predigested rye compared to predigested wheat (8.17 {+/-} 2.71 vs. 6.55 {+/-} 2.16 mmol/l and 3.40 {+/-} 0.436 vs. 2.64 {+/-} 0.337 mmol/l, respectively), whereas butyrate concentrations were not different. Substantial differences were observed between native and predigested substrates with a higher butyrate production on the former. Bacterial cell counts were higher in predigested substrates and elevated in rye cultures compared to respective wheat incubations. Bacterial communities differed markedly between the two predigested cereals as well as between native and predigested substrates. Several known butyrate and propionate producers - for example Agathobacter, Blautia, Coprococcus, Mediterraneibacter and Roseburia - grew significantly more on predigested rye than on predigested wheat. Bifidobacterium, Clostridium sensu stricto, and Succinivibrio were significantly more abundant on native substrates compared to their predigested forms. ConclusionRye promoted higher production of acetate and propionate compared with wheat along with a distinct bacterial community composition. Predigestion of substrates was crucial in in vitro experiments for gaining adequate insights into growth and substrate degradation by colonic microbiota.

microbiology↗

bioRxiv2025

Uncovering differences in rye and wheat degradation by human gut microbiota applying a quantitative multi-metaOmics in vitro approach

While wheat is the most common grain used in bread-making worldwide, rye is popular in many European countries too. Rye is associated with several health benefits, which is attributed to its comparatively higher fiber content (primarily fructans and arabinoxylans) that promote production of short chain fatty acids (SCFA) by gut microbiota, in particular butyrate. Intervention studies revealed bacterial alterations upon rye administration, however, the detailed mechanisms involved in its degradation are not understood. We grew fecal communities (n=20) on pre-digested rye and wheat, respectively, demonstrating that rye was yielding higher cell and SCFA concentrations in almost all samples along with distinct abundances of many taxa. A multi metaOmics (metagenomics/metatranscriptomics) approach (n=5 donors) showed higher bacterial growth rates for most taxa on rye compared to wheat. The higher growth rate of rye was accompanied by increased expression of genes involved in growth and energy generation suggesting higher carbon substrate accessibility. The carbohydrate active enzyme repertoire was greatly distinct between communities growing on the two substrates with several specific glycoside hydrolases increasingly expressed in rye containing cultures. Agathobacter faecis was revealed as the key butyrogenic species for rye degradation and its expression pattern based on metagenome assembled genomes showed adaptation to growth on rye via expression of genes involved in arabinoxylan degradation and fructose (major monomer of fructans) uptake. Our study verifies higher SCFA production from rye over wheat and gives detailed insights into molecular mechanisms involved. It supports that the observed health benefits of rye are mediated by gut microbiota.

microbiology↗

bioRxiv2022

Predicting butyrate- and propionate-forming bacteria of gut microbiota from sequencing data

BackgroundThe bacteria-derived short chain fatty acids (SCFAs) butyrate and propionate play important (distinct) roles in health and disease and understanding the ecology of respective bacteria on a community-wide level is a top priority in microbiome research. The aim of this study was to reveal members harboring main pathways for the production of those metabolites and assess the applicability of sequence data (metagenomics and 16S rRNA gene) to predict SCFAs production in vitro and in vivo. ResultsA clear split between butyrate- and propionate-forming bacteria was detected with only very few taxa exhibiting pathways for the production of both SCFAs. After in vitro growth of fecal communities from distinct donors (n=8) on different substrates (n=7) abundances of bacteria exhibiting pathways correlated with respective SCFA concentrations, in particular in the case of butyrate. While final growth differed markedly between cultures, communities showed high functional redundancies with comparable yields, i.e., concentration of metabolite per grown bacterium exhibiting pathway(s), irrespective of the donor and substrate used. For propionate, correlations were weaker indicating that its production is less imprinted into the core metabolism compared with butyrate-forming bacteria. Longitudinal measurements in vivo (five samples derived from 20 subjects) also revealed a correlation between abundances of pathway-carrying bacteria and concentrations of the two SCFAs. Additionally, lower bacterial cell concentrations, together with higher stool moisture, promoted overall bacterial activity (measured by flow cytometry and coverage patterns of metagenome-assembled genomes) that led to elevated SCFAs concentrations with over-proportional levels of butyrate. Butyrate concentrations displayed lower temporal stability than propionate, however, abundances of bacteria exhibiting the butyrate-forming pathway were more stable than those carrying pathways for propionate production. Predictions on pathway abundances based on 16S rRNA gene data using our in-house database worked well yielding similar results as metagenomic-based analyses. ConclusionsWe demonstrated that pathway abundances enable predictions on concentrations of SCFAs indicating that stimulating bacterial growth directly leads to more production of those compounds. The strong separation of gut microbiota into two functional communities facilitates the development of precision intervention strategies targeting either metabolite.

microbiology↗