Jun Li

The gut microbiota, as a complex ecological system within the host, plays a critical role not only in regulating local intestinal immunity and metabolism but also in influencing hematopoietic stem cell (HSC) function and immune cell lineage differentiation through the gut-bone marrow axis. This review comprehensively examines how the gut microbiota remodels hematopoiesis and immune status via multiple mechanisms, particularly by modulating systemic inflammation, the bone marrow microenvironment, and HSC fate decisions. Special emphasis is placed on the role of Toll-like receptor (TLR) signaling pathways in linking the gut microbiota to bone metabolism and immune regulation. The review also integrates recent insights from single-cell sequencing technologies that reveal hematopoietic lineage biases in the bone marrow and explores the development and immune memory of gut-associated B cell populations during early life. By systematically synthesizing recent advances in the interaction between gut microbiota and bone marrow hematopoiesis, this article aims to provide a theoretical foundation for understanding how gut microbiota regulate systemic immune homeostasis and bone metabolism and to identify potential therapeutic targets for future interventions.

This review synthesizes recent research findings and proposes an integrated “microbiota–metabolite–immune–oncology” framework, highlighting how gut-derived metabolites regulate the dynamics of tumor immunity and informing the development of next-generation immunotherapies. Key metabolites—including short-chain fatty acids (SCFAs), bile acids (BAs), trimethylamine N-oxide (TMAO), indole-3-propionic acid (IPA), and urolithin A—exert bidirectional effects on antitumor immunity through multiple mechanisms. These include histone acetylation-driven epigenetic reprogramming, aryl hydrocarbon receptor (AhR)- and farnesoid X receptor (FXR)-mediated metabolic reprogramming, and direct regulation of immune effectors such as CD8 ⁺ T cells and myeloid-derived suppressor cells. Emerging evidence highlights specific roles of these metabolites within the tumor microenvironment (TME): microbial dysbiosis can amplify immunosuppressive circuits, whereas targeted enrichment of certain metabolites may enhance the efficacy of immune checkpoint blockade. Integrative multi-omics analyses have revealed the vascular remodeling effect of TMAO and the spatiotemporal heterogeneity of BAs, thereby connecting the gut-liver-tumor axis and achieving overall immune regulation. By mapping a precision-oriented metabolic roadmap, this review identifies underexplored therapeutic avenues—such as metabolite-targeted interventions and engineered probiotics—that, when combined with immune checkpoint inhibitors, may enable personalized, microbiome−based strategies with the potential to improve outcomes in cancer immunotherapy.

The bidirectional communication between the gut microbiota (GM) and the enteric nervous system (ENS) is fundamental for gastrointestinal homeostasis. This review dissects the intricate GM–ENS dialogue, emphasizing its transition from a developmental programmer in early life to a sustained regulator of neural plasticity in adulthood. We synthesize the core signaling mechanisms—microbial metabolites, neuroactive substances, and immune mediators—that orchestrate ENS activity. We further propose a multi−timescale model (rapid neuropod/bioelectric, intermediate metabolite, slow immune) with differential relevance to irritable bowel syndrome (IBS) (fast distortions) versus inflammatory bowel disease(IBD)(slow amplification). Critically, we delineate how this axis adopts distinct pathophysiological roles across major digestive disorders: acting as a “signal distorter” in IBS, an “inflammation amplifier” in IBD, and a “tumor accomplice” in colorectal cancer (CRC). By integrating these mechanistic insights with emerging therapeutic paradigms (e.g., precision biomarkers, synthetic microbial consortia, postbiotics), we position the GM–ENS axis as a central hub for understanding disease pathogenesis and a promising framework for developing next-generation precision medicine strategies.

Dysbiosis of the gastric microecology is implicated in various gastric diseases, with Helicobacter pylori ( H. pylori ) infection serving as a pivotal factor influencing the gastric microecological balance and vice versa. In this study, we investigated the novel effects of gastric microbiota transplantation (GMT) on gastric microecology and the potential of this treatment to enhance H. pylori eradication. We performed a metagenomic analysis of the microecological systems across different regions of the stomach, including the gastric fluid (GF), the gastric mucus layer (GML), and the gastric mucosa (GM). We initiated a clinical GMT intervention by transplanting microbial communities from healthy individuals' GML into patients exhibiting refractory H. pylori infection and chronic atrophic gastritis. Our findings demonstrated significant disparities in species richness among the GF, GML, and GM, with the GML exhibiting the highest diversity of unique microbial genera. H. pylori infection primarily influenced the relative species abundance within the GML community, without altering its fundamental composition. Clinically, GMT was well-tolerated by all recipients and showed substantial synergistic efficacy against refractory H. pylori infection, achieving a 100% eradication rate in all patients, and significantly alleviating symptoms in individuals with H. pylori -positive atrophic gastritis ( P < 0.05). Compared with the gastric microbiota of H. pylori -negative patients, the gastric microbiota of H. pylori -positive patients treated with GMT exhibited closer alignment with those of healthy donors. In conclusion, GMT utilizing GML enhanced the eradication rate of refractory H. pylori infection and improved symptoms in patients with H. pylori -positive atrophic gastritis through modulating the gastric microbiota. IMPORTANCE: Dysbiosis of the gastric microecology is implicated in various gastric diseases, with Helicobacter pylori (H. pylori) infection serving as a pivotal factor influencing the gastric microecological balance and vice versa. We investigated the novel effects of gastric microbiota transplantation (GMT) on gastric microecology and the potential of this treatment to enhance H. pylori eradication. GMT significantly enhanced the eradication rate of refractory H. pylori infection and improved symptoms in patients with H. pylori -positive atrophic gastritis. GMT demonstrated improvements in the cure rate of refractory H. pylori infection, potentially offering a new clinical treatment approach. This finding provides new insights and a potential therapeutic direction for treating dysbiosis related chronic gastric diseases.

Candida albicans is an opportunistic pathogen that resides in the human gut alongside a diverse array of microorganisms, including enteric bacteria, archaea, and viruses, which collectively form the gut microbiota. Recent studies have shown that the development of Candida albicans infections involves both weakened host immunity and enhanced invasiveness of Candida albicans, with intestinal microecology serving as a critical mediator of these processes. It has been demonstrated that disturbances in the gut microbiome can potentiate the invasive capacity of Candida albicans. Moreover, a compromised immune system, along with the use of antibiotics and immunosuppressive drugs, can lead to gut microbiome imbalances. Consequently, modulators of the intestinal microecology represent promising therapeutic interventions for managing Candida albicans infections. In this review, we examine the mechanisms underlying the increased invasiveness of Candida albicans following significant disruption of intestinal bacteria and highlighting the interplay among immune dysfunction, antibiotic use, and their effects on gut microbiome imbalance and Candida albicans infection. Additionally, we summarize the roles of microbiome-based therapies, such as probiotics, prebiotics, dietary interventions, and fecal microbiota transplantation (FMT), in addressing Candida albicans infections. This review provides a theoretical foundation and practical guidance for the development of more effective microecological therapeutic strategies in the future.

Introduction: Despite the established influence of gut bacteria, the role of the gut virome in modulating colorectal cancer (CRC) patient chemotherapy response remains poorly understood. In this study, we investigated the impact of antiviral (AV) drug-induced gut virome dysbiosis on the efficacy of 5-FU in CRC treatment.Methods: Using a subcutaneous CRC mouse model, we assessed tumor growth and immune responses following AV treatment, fecal microbiota transplantation (FMT), and 5-FU administration.Results: AV therapy reduced the abundance of gut DNA and RNA viruses, leading to accelerated tumor growth, shortened survival, and diminished chemotherapy efficacy. FMT restored the gut virome, improving tumor suppression and extending the survival of 5-FU-treated mice. Metagenomic sequencing revealed significant changes in virome composition, AV treatment expanded Kahnovirus, Petivirales, and Enterogokushovirus, whereas FMT enriched Peduovirus STYP1, Mahlunavirus rarus, and Jouyvirus ev207. AV treatment reduced the number of dendritic cells and CD8+ T cells in peripheral blood and tumor tissues, impairing antitumor immunity, FMT reversed these deficiencies. To further investigate the underlying mechanisms, we examined the TLR3-IRF3-IFN-β pathway, essential for recognizing viral RNA and triggering immune responses. AV treatment downregulated this pathway, impairing immune cell recruitment and reducing chemotherapy efficacy, while activation of TLR3 with Poly(I:C) restored pathway function and enhanced the effectiveness of 5-FU.Discussion: These findings suggest the importance of maintaining gut virome integrity or activating TLR3 as adjunct strategies to enhance chemotherapy outcomes in CRC patients.

The gut mycobiome significantly affects host health and immunity. However, most studies have focused on symbiotic bacteria in the gut microbiome, whereas less attention has been given to symbiotic fungi. Although fungi constitute only 0.01%-0.1% of the gut microbiome, their larger size and unique immunoregulatory functions make them significant. Factors like diet, antimicrobials use, and age can disrupt the fungal community, leading to dysbiosis. Fungal-bacterial-host immune interactions are critical in maintaining gut homeostasis, with fungi playing a role in mediating immune responses such as Th17 cell activation. This review highlights methods for studying gut fungi, the composition and influencing factors of the gut mycobiome, and its potential in therapeutic interventions for intestinal and hepatic diseases. We aim to provide new insights into the underexplored role of gut fungi in human health.

The human gut harbors a complex and diverse microbiota essential for maintaining health. Diet is the most significant modifiable factor influencing gut microbiota composition and function, particularly through bioactive compounds like polyphenols, dietary fibers, and carotenoids found in vegetables, fruits, seafood, coffee, and green tea. These compounds regulate the gut microbiota by promoting beneficial bacteria and suppressing harmful ones, leading to the production of key microbiota-derived metabolites such as short-chain fatty acids, bile acid derivatives, and tryptophan metabolites. These metabolites are crucial for gut homeostasis, influencing gut barrier function, immune responses, energy metabolism, anti-inflammatory processes, lipid digestion, and modulation of gut inflammation. This review outlines the regulatory impact of typical bioactive compounds on the gut microbiota and explores the connection between specific microbiota-derived metabolites and overall health. We discuss how dietary interventions can affect disease development and progression through mechanisms involving these metabolites. We examine the roles of bioactive compounds and their metabolites in the prevention and treatment of diseases including inflammatory bowel disease, colorectal cancer, cardiovascular diseases, obesity, and type 2 diabetes mellitus. This study provides new insights into disease prevention and underscores the potential of dietary modulation of the gut microbiota as a strategy for improving health.

Aim: To explore the complex relationship between gut microbiota, obesity-related male reproductive impairments, and the NLRP3 inflammasome. Methods: A high-fat diet was administered to induce obesity in a mouse model, fecal microbiota transplantation or a high-dietary fiber diet (HDFD) was administered for 5 weeks to evaluate changes in parameters related to reproductive capacity, NLRP3, gut microbiota composition and metabolites in mice. Results: A high-fat diet induces obesity and decreases reproductive capacity in male mice. Fecal microbiota transplantation and HDFD can improve reproductive capacity in obese mice by adjusting the gut microbiota population to suppress the NLRP3/ASC/caspase-1 axis, thereby reducing IL-1 beta levels. Conclusion: This study offers a potential treatment for obesity-induced reproductive dysfunction by targeting the gut microbiota and the NLRP3 inflammasome pathway. PLAIN LANGUAGE SUMMARY This study looks at how gut bacteria, obesity and our immune system affect male reproductive health. We made mice obese by feeding them a high-fat diet. Then, we treated them with either a transplant of gut bacteria or a high-fiber diet for 5 weeks. We found that the high-fat diet made it harder for male mice to have babies. Both the transplant and the high-fiber diet helped improve their ability to reproduce. Changing the bacteria in their gut reduced inflammation by affecting the immune system. Our findings suggest that changing gut bacteria and focusing on this part of the immune system could help with reproductive problems caused by obesity.