Flavonifractor plautii as a Next-Generation Probiotic Enhancing the NGP F/P Index in a Simulated Human Gut Microbiome Ecosystem

<b>Background/Objectives</b>: Traditionally consumed fermented foods and lactic acid bacteria (LAB)-based products have primarily been investigated for their nutritional and health-promoting benefits as dietary supplements. More recently, research has advanced toward exploring their therapeutic potential in pharmaceutical development. However, reliance on conventional LAB strains despite their established safety and efficacy has led to saturation at the strain level, underscoring the need for next-generation probiotics (NGPs) with novel therapeutic potential. In this context, we identified <i>Flavonifractor plautii</i> from human feces as a candidate NGP and investigated its effects on the human gut microbiota. <b>Methods</b>: Whole-genome sequencing revealed distinct genetic features that supported its uniqueness, and the strain was designated PMC93. A human gut microbial ecosystem simulator was used to administer <i>F. plautii</i> daily for one week, after which microbial community changes were evaluated using 16S rRNA gene-based metagenomic sequencing. <b>Results</b>: The administration did not induce significant changes in alpha or beta diversity, suggesting that <i>F. plautii</i> does not disrupt overall bacterial community structure, thereby supporting its microbial community safety. Taxonomic analysis demonstrated a significant increase in the <i>Firmicutes</i>-to-<i>Proteobacteria</i> ratio (NGP F/P index). The improvement surpassed that of conventional LAB treatments and was consistently maintained under supplementation with commonly encountered pharmaceutical compounds and nutrients. The shift was associated with an increase in short-chain fatty acid (SCFA)-producing beneficial taxa and a decrease in pro-inflammatory and potentially pathogenic groups. Functional outcomes, including elevated SCFA levels and downregulation of inflammation-related gene expression, further corroborated these compositional changes. The strain also demonstrated safety in in vivo models. <b>Conclusions</b>: Collectively, these findings suggest that strain PMC93 is a promising NGP candidate with substantial therapeutic potential for microbiota-associated health and disease modulation, particularly due to its ability to enhance the NGP F/P index.