Background/Objectives: 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 Flavonifractor plautii from human feces as a candidate NGP and investigated its effects on the human gut microbiota. Methods: 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 F. plautii daily for one week, after which microbial community changes were evaluated using 16S rRNA gene-based metagenomic sequencing. Results: The administration did not induce significant changes in alpha or beta diversity, suggesting that F. plautii does not disrupt overall bacterial community structure, thereby supporting its microbial community safety. Taxonomic analysis demonstrated a significant increase in the Firmicutes-to-Proteobacteria 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. Conclusions: 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.

Xerosis, characterized by dry, rough skin, causes discomfort and aesthetic concerns, necessitating effective treatment. Traditional treatments often show limited efficacy, prompting the need for innovative therapies. This study highlights the efficacy of microbiome therapeutic LP51, derived from a healthy vaginal microbiome, in improving xerosis. A double-blind clinical trial involving 43 subjects with dry inner arm skin compared the effects of a 2.9% LP51 extract formulation to a placebo over 4 weeks. The LP51 group exhibited a significant increase in stratum corneum hydration (10.0 A.U.) compared to the placebo group (4.8 A.U.) and a 21.4% decrease in transepidermal water loss (TEWL), whereas the placebo group showed no significant change. LP51 also demonstrated benefits in enhancing skin hydration, improving the skin barrier, and exhibited anti-atopic, anti-inflammatory, and antioxidant properties. Safety was confirmed through in vitro cytotoxicity tests. These effects are attributed to the microbiome-safe component in LP51 and its role in improving xerosis, reflected by an increase in the xerosis-microbiome index, defined by the Firmicutes/Actinobacteria ratio. These findings position microbiome therapeutic LP51 as a promising novel treatment for xerosis.

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.

With the growing interest in the microbiome, short-chain fatty acids (SCFAs) have emerged as key metabolites due to their critical roles in host physiology, including immune regulation, energy homeostasis, and inflammatory control. As a result, the accurate quantification of SCFAs in various biological samples has become increasingly important. However, reliable and standardized methods for measuring SCFAs across different sample types remain underdeveloped, highlighting the need for methodological refinement. To address this need, we optimized two analytical methods, headspace GC-MS and GC-MS/MS, for SCFA quantification. These techniques were applied to a range of biological matrices, including pure microbial cultures, low-abundance animal liver, animal feces, and standardized simulated human fecal samples. The headspace GC-MS approach enables direct analysis with minimal sample preparation, thereby enhancing throughput and ease of use. In contrast, the GC-MS/MS method, involving methanol extraction, alkaline treatment, and derivatization with MTBSTFA, offers superior sensitivity and precision, making it particularly suitable for small-volume and low-abundance samples. Together, these optimized protocols provide robust, sensitive platforms for profiling SCFAs across diverse biological matrices, facilitating a deeper understanding of microbiome–host interactions and supporting future translational applications.