Enhancement of Gut Microbial Homeostasis by a Post-NGP Phocaeicola vulgatus

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Background: Humans have long consumed lactic acid bacteria-based fermented foods, and this empirical experience has led to the development of probiotic-based functional foods and therapeutics. However, conventional development strategies have largely focused on commonly used probiotic strains to prioritize development efficiency and safety, resulting in limited functional innovation. Although research on next-generation probiotics (NGPs) has expanded in recent years, there is an increasing need for post-next-generation probiotic (Post-NGP) strategies that address subsequent stages of microbiome modulation. Methods: In this study, Phocaeicola vulgatus PMC94 was isolated and characterized as a Post-NGP candidate, and its effects on gut microbiome balance were evaluated using ex vivo human gut microbiota culture (ex vivo HGMC). Results: Dysbiosis induced by commonly encountered therapeutic agents was significantly alleviated by co-administration of PMC94. This restorative effect on gut microbiome imbalance was more pronounced than that observed with conventional probiotic strains. To elucidate the mechanistic basis underlying these effects, additional analyses were conducted using a human gut microbiome simulator (HGMS). PMC94 selectively suppressed Proteobacteria while promoting balanced proliferation of Bacteroidetes and Firmicutes, thereby restoring gut microbial homeostasis. This pattern of microbiome modulation was consistently supported by in vivo mouse experiments. Furthermore, these changes were associated with increased production of short-chain fatty acids (SCFAs), as well as immune modulation and reinforcement of gut barrier function. The safety of PMC94 was confirmed through a 2-week repeated-dose toxicity study. Conclusions: Collectively, these findings demonstrate that P. vulgatus PMC94 is a promising Post-NGP candidate capable of restoring and strengthening gut microbial homeostasis.

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