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Insights from shotgun metagenomics into bacterial species and metabolic pathways associated with NAFLD in obese youth.

ABSTRACT: Nonalcoholic fatty liver disease (NAFLD) is the most common form of liver disease and is often the precursor for more serious liver conditions such as nonalcoholic steatohepatitis and cirrhosis. Although the gut microbiome has been implicated in the development of NAFLD, the strong association of obesity with NAFLD and its effect on microbiome structure has made interpreting study outcomes difficult. In the present study, we examined the taxonomic and functional differences between the microbiomes of youth with obesity and with and without NAFLD. Shotgun metagenome sequencing was performed to profile the microbiomes of 36 subjects, half of whom were diagnosed with NAFLD using abdominal magnetic resonance imaging. Beta diversity analysis showed community-wide differences between the groups (p = 0.002). Specific taxonomic differences included increased relative abundances of the species Fusicatenibacter saccharivorans (p = 0.042), Romboutsia ilealis (p = 0.046), and Actinomyces sp. ICM47 (p = 0.0009), and a decrease of Bacteroides thetaiotamicron (p = 0.0002), in the NAFLD group as compared with the non-NAFLD group. At the phylum level, Bacteroidetes (p < 0.0001) was decreased in the NAFLD group. Functionally, branched-chain amino acid (p = 0.01343) and aromatic amino acid (p = 0.01343) synthesis pathways had increased relative abundances in the NAFLD group along with numerous energy use pathways, including pyruvate fermentation to acetate (p = 0.01318). Conclusion: Community-wide differences were noted based on NAFLD status, and individual bacterial species along with specific metabolic pathways were identified as potential drivers of these differences. The results of the present study support the idea that the NAFLD phenotype displays a differentiated microbial and functional signature from the obesity phenotype.

SUBMITTER: Testerman T

PROVIDER: S-EPMC9315112 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Water kefir is a fruity, sour, slightly alcoholic and carbonated beverage, which is made by fermentation of an aqueous sucrose solution in the presence of dried figs and water kefir grains. These polysaccharide grains contain lactic acid bacteria (LAB), yeasts, and sometimes bifidobacteria and/or acetic acid bacteria, which consume sucrose to produce exopolysaccharides, lactic acid, acetic acid, ethanol, and carbon dioxide. Shotgun metagenomic sequencing was used to examine the microbial species diversity present at two time points during water kefir fermentation in detail, both in the water kefir liquor and on the water kefir grains, hence representing four samples. Lactobacillus harbinensis, Lactobacillus hilgardii, Lactobacillus nagelii, Lactobacillus paracasei, and a Lactobacillus species similar to Lactobacillus hordei/mali were present in the water kefir examined, along with Bifidobacterium aquikefiri and two yeast species, namely Saccharomyces cerevisiae and Dekkera bruxellensis. In addition, evidence for a novel Oenococcus species related to Oenococcus oeni and Oenococcus kitaharae was found. Its genome was derived from the metagenome and made available under the name of Candidatus Oenococcus aquikefiri. Through functional analysis of the four metagenomic data sets, it was possible to link the production of lactic acid, acetic acid, ethanol, and carbon dioxide to subgroups of the microbial species found. In particular, the production of mannitol from fructose was linked to L. hilgardii, Candidatus O. aquikefiri, and B. aquikefiri, whereas glycerol production was associated with S. cerevisiae. Also, there were indications of cross-feeding, for instance in the case of amino acid supply. Few bacterial species could synthesize a limited number of cofactors, making them reliant on the figs or S. cerevisiae. The LAB species in turn were found to be capable of contributing to water kefir grain growth, as dextransucrase-encoding genes were attributed to L. hilgardii, L. hordei/mali, and Candidatus O. aquikefiri.

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Insights from shotgun metagenomics into bacterial species and metabolic pathways associated with NAFLD in obese youth.

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