Diet-dependent effects of kombucha on the gut microbiome and its neuroactive potential: Associations with reduced anxiety and depressive-like behaviors in mice

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This study found that kombucha supplementation altered the gut microbiome and neuroactive metabolism in mice, leading to diet-dependent reductions in anxiety and depressive-like behaviors.

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This study tested, in male C57BL/6 mice fed either a total Western diet or a control diet, whether kombucha supplementation (three times weekly for seven weeks) reshaped the gastrointestinal microbiome and altered stress-related behaviors, alongside gut and brain metabolic profiling. Using behavioral assays (forced swimming and marble burying), multi-site microbiome sequencing/metagenomics, LC-MS metabolomics of feces and whole brains, and serum cytokine measurements, the authors found that kombucha reduced immobility in the forced swimming test under both diets, while it reduced marble burying only in the Western-diet group. Microbiome and metabolite effects were diet-dependent, including kombucha-associated increases in Bifidobacterium pseudolongum in the ileum under both diets and, only under the control diet, higher fecal acetate and butyrate with lower fecal neurochemically relevant amino acids; under the Western diet, kombucha was linked to altered brain tryptophan/kynurenine profiles. The paper does not explicitly discuss endometriosis or adenomyosis; it was included in the corpus via a keyword match in the upstream search index.

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Abstract

ABSTRACT Fermented foods are increasingly recognized for their health-boosting potential, yet the mechanisms involved are not fully resolved. Here, we tested whether kombucha reshapes the gastrointestinal microbiome and whether these changes are associated with stress-related behaviors under contrasting dietary backgrounds. Male C57BL/6 mice were fed either a total Western diet (TWD) or a control diet (CTRL) supplemented with kombucha or water three times weekly for seven weeks. Depressive-like and anxiety-related behaviors were evaluated using the forced swimming (FST) and marble burying tests (MBT). Ileum, cecum, and colon microbiomes were profiled via 16S rRNA, ITS2, and shotgun metagenomics, while feces and whole brains were profiled by LC-MS metabolomics. Serum cytokines were measured by ELISA. Results highlight diet-dependent effects of Kombucha on behavioral, microbial and metabolic outcomes. Kombucha reduced immobility in the FST under both diets, whereas fewer marbles buried were observed only under TWD. Kombucha intake enriched Bifidobacterium pseudolongum in the ileum under CTRL and TWD diets, while cecal microbial functions related to amino acid metabolism were stimulated mainly under CTRL. Only CTRL mice receiving kombucha showed higher fecal acetate and butyrate together with lower fecal levels of neurochemically relevant amino acids, including glutamine, phenylalanine, tryptophan, and tyrosine. Under TWD, kombucha was associated with lower spleen weight and altered brain tryptophan/kynurenine profiles. These findings identify kombucha as a food intervention that can remodel gastrointestinal microbial and neuroactive metabolism in a diet depending manner. Associations with reduced depressive and anxiety-related behaviors are promising but warrant further exploration. Key Highlights Kombucha supplementation reshaped the mice gastrointestinal microbiome and its neuroactive potential Kombucha intake was associated reduced depressive and anxious like behaviors The potential of kombucha to modulate microbial, metabolic and behavioral outcomes may be dependent on subject dietary background
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ABSTRACT Fermented foods are increasingly recognized for their health-boosting potential, yet the mechanisms involved are not fully resolved. Here, we tested whether kombucha reshapes the gastrointestinal microbiome and whether these changes are associated with stress-related behaviors under contrasting dietary backgrounds. Male C57BL/6 mice were fed either a total Western diet (TWD) or a control diet (CTRL) supplemented with kombucha or water three times weekly for seven weeks. Depressive-like and anxiety-related behaviors were evaluated using the forced swimming (FST) and marble burying tests (MBT). Ileum, cecum, and colon microbiomes were profiled via 16S rRNA, ITS2, and shotgun metagenomics, while feces and whole brains were profiled by LC-MS metabolomics. Serum cytokines were measured by ELISA. Results highlight diet-dependent effects of Kombucha on behavioral, microbial and metabolic outcomes. Kombucha reduced immobility in the FST under both diets, whereas fewer marbles buried were observed only under TWD. Kombucha intake enriched Bifidobacterium pseudolongum in the ileum under CTRL and TWD diets, while cecal microbial functions related to amino acid metabolism were stimulated mainly under CTRL. Only CTRL mice receiving kombucha showed higher fecal acetate and butyrate together with lower fecal levels of neurochemically relevant amino acids, including glutamine, phenylalanine, tryptophan, and tyrosine. Under TWD, kombucha was associated with lower spleen weight and altered brain tryptophan/kynurenine profiles. These findings identify kombucha as a food intervention that can remodel gastrointestinal microbial and neuroactive metabolism in a diet depending manner. Associations with reduced depressive and anxiety-related behaviors are promising but warrant further exploration. Key Highlights Kombucha supplementation reshaped the mice gastrointestinal microbiome and its neuroactive potential Kombucha intake was associated reduced depressive and anxious like behaviors The potential of kombucha to modulate microbial, metabolic and behavioral outcomes may be dependent on subject dietary background Competing Interest Statement The authors have declared no competing interest.

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