Background: The involvement of the intratumoral microbiome in prostate cancer progression is becoming increasingly acknowledged. This study analyzed the microbiome of prostate cancer tissues from patients with localized prostate cancer (LPC, stages 1–2) and advanced prostate cancer (APC, stages 3–4) to determine its association with cancer progression. Methods: Paraffin-embedded tissue samples obtained during radical prostatectomy underwent 16S rRNA amplicon-based profiling. Results: The profile of the bacterial communities in LPC and APC differed remarkably. While species diversity remained stable, species richness (as determined by the ACE analysis) was significantly lower in APC, correlating with a decrease in Enhydrobacter (which is more abundant in LPC) and an increase in Lautropia (enriched in APC). The role of Lautropia in the progression of cancer was confirmed by in vitro studies employing cell lines from prostate cancer. Conclusions: These findings demonstrate the potential of microbiome-targeted interventions in the management of prostate cancer.

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.

Numerous human pathologies, such as neoplasia, are related to particular bacteria and changes in microbiome constituents. To investigate the association between an imbalance of bacteria and prostate carcinoma, the microbiome and gene functionality from tissues of patients with high-grade prostate tumor (HGT) and low-grade prostate tumor (LGT) were compared utilizing next-generation sequencing (NGS) technology. The results showed abnormalities in the bacterial profiles between the HGT and LGT specimens, indicating alterations in the make-up of bacterial populations and gene functionalities. The HGT specimens showed higher frequencies of Cutibacterium, Pelomonas, and Corynebacterium genera than the LGT specimens. Cell proliferation and cytokine assays also showed a significant proliferation of prostate cancer cells and elevated cytokine levels in the cells treated with Cutibacterium, respectively, supporting earlier findings. In summary, the HGT and LGT specimens showed differences in bacterial populations, suggesting that different bacterial populations might characterize high-grade and low-grade prostate malignancies.

Tuberculosis, primarily caused by Mycobacterium tuberculosis, is an airborne lung disease and continues to pose a significant global health threat, resulting in millions of deaths annually. The current treatment for tuberculosis involves a prolonged regimen of antibiotics, which leads to complications such as recurrence, drug resistance, reinfection, and a range of side effects. This scenario underscores the urgent need for novel therapeutic strategies to combat this lethal pathogen. Over the last two decades, microbiome therapeutics have emerged as promising next-generation drug candidates, offering advantages over traditional medications. In 2022, the Food and Drug Administration approved the first microbiome therapeutic for recurrent Clostridium infections, and extensive research is underway on microbiome treatments for various challenging diseases, including metabolic disorders and cancer. Research on microbiomes concerning tuberculosis commenced roughly a decade ago, and the scope of this research has broadened considerably over the last five years, with microbiome therapeutics now viewed as viable options for managing drug-resistant tuberculosis. Nevertheless, the understanding of their mechanisms is still in its infancy. Although autophagy has been extensively studied in other diseases, research into its role in tuberculosis is just beginning, with preliminary developments in progress. Against this backdrop, this comprehensive review begins by succinctly outlining tuberculosis’ characteristics and assessing existing treatments’ strengths and weaknesses, followed by a detailed examination of microbiome-based therapeutic approaches for drug-resistant tuberculosis. Additionally, this review focuses on establishing a basic understanding of microbiome treatments for tuberculosis, mainly through the lens of autophagy as a mechanism of action. Ultimately, this review aims to contribute to the foundational comprehension of microbiome-based therapies for tuberculosis, thereby setting the stage for the further advancement of microbiome therapeutics for drug-resistant tuberculosis.

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.