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Variation and transmission of the human gut microbiota across multiple familial generations.

ABSTRACT: Although the composition and functional potential of the human gut microbiota evolve over the lifespan, kinship has been identified as a key covariate of microbial community diversification. However, to date, sharing of microbiota features within families has mostly been assessed between parents and their direct offspring. Here we investigate the potential transmission and persistence of familial microbiome patterns and microbial genotypes in a family cohort (n = 102) spanning 3 to 5 generations over the same female bloodline. We observe microbiome community composition associated with kinship, with seven low abundant genera displaying familial distribution patterns. While kinship and current cohabitation emerge as closely entangled variables, our explorative analyses of microbial genotype distribution and transmission estimates point at the latter as a key covariate of strain dissemination. Highest potential transmission rates are estimated between sisters and mother-daughter pairs, decreasing with increasing daughter's age and being higher among cohabiting pairs than those living apart. Although rare, we detect potential transmission events spanning three and four generations, primarily involving species of the genera Alistipes and Bacteroides. Overall, while our analyses confirm the existence of family-bound microbiome community profiles, transmission or co-acquisition of bacterial strains appears to be strongly linked to cohabitation.

SUBMITTER: Valles-Colomer M

PROVIDER: S-EPMC8727295 | biostudies-literature | 2022 Jan

REPOSITORIES: biostudies-literature

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Variation and transmission of the human gut microbiota across multiple familial generations.

Valles-Colomer Mireia M Bacigalupe Rodrigo R Vieira-Silva Sara S Suzuki Shinya S Darzi Youssef Y Tito Raul Y RY Yamada Takuji T Segata Nicola N Raes Jeroen J Falony Gwen G

Nature microbiology 20211230 1

Although the composition and functional potential of the human gut microbiota evolve over the lifespan, kinship has been identified as a key covariate of microbial community diversification. However, to date, sharing of microbiota features within families has mostly been assessed between parents and their direct offspring. Here we investigate the potential transmission and persistence of familial microbiome patterns and microbial genotypes in a family cohort (n = 102) spanning 3 to 5 generations ...[more]

PMID: 34969979

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Project description:Tamoxifen is the most prescribed drug used to prevent breast cancer recurrence, but patients show variable responses to tamoxifen. Such differential inter-individual response has a significant socioeconomic impact as one in eight women will develop breast cancer and nearly half a million people in the United States are treated with tamoxifen annually. Tamoxifen is orally delivered and must be activated by metabolizing enzymes in the liver; however, clinical studies show that neither genotype nor hepatic metabolic enzymes are sufficient to predict why some patients have sub-therapeutic levels of the drug. Here, using gnotobiotic- and antibiotics-treated mice, we show that tamoxifen pharmacokinetics are heavily influenced by gut bacteria and prolonged exposure to tamoxifen. Interestingly, 16S rRNA gene sequencing shows tamoxifen does not affect overall microbiota composition and abundance. Metabolomics, however, reveals differential metabolic profiles across the microbiomes of different donors cultured with tamoxifen, suggesting an enzymatic diversity within the gut microbiome that influences response to tamoxifen. Consistent with this notion, we found that β-glucuronidase (GUS) enzymes vary in their hydrolysis activity of glucuronidated tamoxifen metabolites across the gut microbiomes of people. Together, these findings highlight the importance of the gut microbiome in tamoxifen's pharmacokinetics.IMPORTANCEOne in eight women will develop breast cancer in their lifetime, and tamoxifen is used to suppress breast cancer recurrence, but nearly 50% of patients are not effectively treated with this drug. Given that tamoxifen is orally administered and, thus, reaches the intestine, this variable patient response to the drug is likely related to the gut microbiota composed of trillions of bacteria, which are remarkably different among individuals. This study aims to understand the impact of the gut microbiome on tamoxifen absorption, metabolism, and recycling. The significance of our research is in defining the role that gut microbes play in tamoxifen pharmacokinetics, thus paving the way for more tailored and effective therapeutic interventions in the prevention of breast cancer recurrence.

Dataset Information

Variation and transmission of the human gut microbiota across multiple familial generations.

Publications

Variation and transmission of the human gut microbiota across multiple familial generations.

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