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Dietary Exposure to Antibiotic Residues Facilitates Metabolic Disorder by Altering the Gut Microbiota and Bile Acid Composition.

ABSTRACT: Antibiotics used as growth promoters in livestock and animal husbandry can be detected in animal-derived food. Epidemiological studies have indicated that exposure to these antibiotic residues in food may be associated with childhood obesity. Herein, the effect of exposure to a residual dose of tylosin-an antibiotic growth promoter-on host metabolism and gut microbiota was explored in vivo. Theoretical maximal daily intake (TMDI) doses of tylosin were found to facilitate high-fat-diet-induced obesity, induce insulin resistance, and perturb gut microbiota composition in mice. The obesity-related phenotypes were transferrable to germfree recipient mice, indicating that the effects of a TMDI dose of tylosin on obesity and insulin resistance occurred mainly via alteration of the gut microbiota. Tylosin TMDI exposure restricted to early life, the critical period of gut microbiota development, altered the abundance of specific bacteria related to host metabolic homeostasis later in life. Moreover, early-life exposure to tylosin TMDI doses was sufficient to modify the ratio of primary to secondary bile acids, thereby inducing lasting metabolic consequences via the downstream FGF15 signaling pathway. Altogether, these findings demonstrate that exposure to very low doses of antibiotic residues, whether continuously or in early life, could exert long-lasting effects on host metabolism by altering the gut microbiota and its metabolites. IMPORTANCE This study demonstrates that even with limited exposure in early life, a residual dose of tylosin might cause long-lasting metabolic disturbances by altering the gut microbiota and its metabolites. Our findings reveal that the gut microbiota is susceptible to previously ignored environmental factors.

SUBMITTER: Chen RA

PROVIDER: S-EPMC9239188 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:BackgroundNormal mammalian development and homeostasis are dependent upon the gut microbiota. Antibiotics, essential for the treatment and prophylaxis of bacterial infections, can have collateral effects on the gut microbiota composition, which can in turn have far-reaching and potentially deleterious consequences for the host. However, the magnitude and duration of such collateral effects appear to vary between individuals. Furthermore, the degree to which such perturbations affect the host response is currently unclear. We aimed to test the hypothesis that different human microbiomes have different responses to a commonly prescribed antibiotic and that these differences may impact the host response.MethodsGerm-free mice (n = 30) humanized with the microbiota of two unrelated donors (A and B) were subjected to a 7-day antibiotic challenge with amoxicillin-clavulanate ("co-amoxiclav"). Microbiome and colonic transcriptome analysis was performed, pre (day 0) and post antibiotics (day 8) and subsequently into recovery (days 11 and 18).ResultsUnique community profiles were evident depending upon the donor, with donor A recipient mice being dominated by Prevotella and Faecalibacterium and donor B recipient mice dominated by Bacteroides and Parabacteroides. Donor A mice underwent a marked destabilization of their microbiota following antibiotic treatment, while donor B mice maintained a more stable profile. Dramatic and overlapping alterations in the host transcriptome were apparent following antibiotic challenge in both groups. Despite this overlap, donor A mice experienced a more significant alteration in gene expression and uniquely showed correlations between host pathways and key microbial genera.ConclusionsGerm-free mice humanized by different donor microbiotas maintain distinct microbiome profiles, which respond in distinct ways to antibiotic challenge and evince host responses that parallel microbiome disequilibrium. These results suggest that inter-individual variation in the gut microbiota may contribute to personalized host responses following microbiota perturbation.

Project description:The structure and diversity of human gut microbiota are directly related to diet, though less is known about the influences of ethnicity and diet-related behaviors, such as fasting (intermittent caloric restriction). In this study, we investigated whether fasting for Ramadan altered the microbiota in Chinese and Pakistani individuals. Using high-throughput 16S rRNA gene sequencing and self-reported dietary intake surveys, we determined that both the microbiota and dietary composition were significantly different with little overlap between ethnic groups. Principal Coordinate Analyses (PCoA) comparison of samples collected from both groups before and after fasting showed partial separation of microbiota related to fasting in the Pakistani group, but not in the Chinese group. Measurement of alpha diversity showed that Ramadan fasting significantly altered the coverage and ACE indices among Chinese subjects, but otherwise incurred no changes among either group. Specifically, Prevotella and Faecalibacterium drove predominance of Bacteroidetes and Firmicutes in the Pakistani group, while Bacteroides (phylum Bacteroidetes) were the most prevalent among Chinese participants both before and after fasting. We observed significant enrichment of some specific taxa and depletion of others in individuals of both populations, suggesting that fasting could affect beta diversity. Notably, Dorea, Klebsiella, and Faecalibacterium were more abundant in the Chinese group after fasting, while Sutterella, Parabacteroides, and Alistipes were significantly enriched after fasting in the Pakistani group. Evaluation of the combined groups showed that genera Coprococcus, Clostridium_XlV, and Lachnospiracea were all significantly decreased after fasting. Analysis of food intake and macronutrient energy sources showed that fat-derived energy was positively associated with Oscillibacter and Prevotella, but negatively associated with Bacteroides. In addition, the consumption of sweets was significantly positively correlated with the prevalence of Akkermansia. Our study indicated that diet was the most significant influence on microbiota, and correlated with ethnic groups, while fasting led to enrichment of specific bacterial taxa in some individuals. Given the dearth of understanding about the impacts of fasting on microbiota, our results provide valuable inroads for future study aimed at novel, personalized, behavior-based treatments targeting specific gut microbes for prevention or treatment of digestive disorders.

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Dietary Exposure to Antibiotic Residues Facilitates Metabolic Disorder by Altering the Gut Microbiota and Bile Acid Composition.

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