The human gut microbiome plays a crucial role in regulating intestinal and systemic health, impacting host immune response and metabolic function. Dysbiosis of the gut microbiome is linked to various diseases, including steatotic liver diseases. Metabolic dysfunction‐associated steatotic liver disease (MASLD), a chronic liver disease characterized by excess hepatic lipid content and impaired metabolism, is the leading cause of liver disease worldwide. Among the gut microbes, Ruminococcus gnavus (R. gnavus) has garnered attention for its association with inflammatory and metabolic diseases. While R. gnavus abundance correlates to liver fat accumulation, further research is needed to identify a causal role or therapeutic intervention in steatotic liver disease. This review surveys our current understanding of R. gnavus in the development and progression of steatotic liver diseases, highlighting its potential mechanisms through metabolite secretion, and emphasizes the need for comprehensive microbiome analyses and longitudinal studies to better understand R. gnavus' impact on liver health. This knowledge could pave the way for targeted interventions aimed at modulating gut microbiota to treat and prevent MASLD and its comorbidities.

Our body composition is enormously influenced by our lifestyle choices, which affect our health and longevity. Nutrition and physical activities both impact overall metabolic condition, thus, a positive energy balance causes oxidative stress and inflammation, hastening the development of metabolic syndrome. With this knowledge, boosting endogenous and exogenous antioxidants has emerged as a therapeutic strategy for combating metabolic disorders. One of the promising therapeutic inventions is the use of alkaline reduced water (ARW). Aside from its hydrating and non-caloric properties, ARW has demonstrated strong antioxidant and anti-inflammatory properties that can help stabilize physiologic turmoil caused by oxidative stress and inflammation. This review article is a synthesis of studies where we elaborate on the intra- and extracellular effects of drinking ARW, and relate these to the pathophysiology of common metabolic disorders, such as obesity, diabetes mellitus, non-alcoholic fatty liver disease, and some cancers. Highlighting the health-promoting benefits of ARW, we also emphasize the importance of maintaining a healthy lifestyle by incorporating exercise and practicing a balanced diet as forms of habit.

This study identifies a novel probiotic-driven mechanism linking dietary tryptophan and host arginine metabolism. Lacticaseibacillus rhamnosus GG, in synergy with tryptophan, enhances gut barrier integrity by upregulating argininosuccinate lyase (ASL), a critical enzyme in arginine biosynthesis. Furthermore, we uncover ASL downregulation and serum argininosuccinate elevation in experimental colitis in mice, suggesting a target to guide precision probiotics.

Ruminococcus gnavus is a mucolytic commensal bacterium whose increased gut colonization has been associated with chronic inflammatory and metabolic diseases in humans. Whether R. gnavus metabolites can modulate host intestinal physiology remains largely understudied. We performed untargeted metabolomic and bulk RNA-seq analyses using R. gnavus monocolonization in germ-free mice. Based on transcriptome-metabolome correlations, we tested the impact of specific arginine metabolites on intestinal epithelial production of nitric oxide (NO) and examined the effect of NO on the growth of various strains of R. gnavus in vitro and in nitric oxide synthase 2 (Nos2)-deficient mice. R. gnavus produces specific arginine, tryptophan, and tyrosine metabolites, some of which are regulated by the environmental richness of sialic acid and mucin. R. gnavus colonization promotes expression of amino acid transporters and enzymes involved in metabolic flux of arginine and associated metabolites into NO. R. gnavus induced elevated levels of NOS2, while Nos2 ablation resulted in R. gnavus expansion in vivo. The growth of various R. gnavus strains can be inhibited by NO. Specific R. gnavus metabolites modulate intestinal epithelial cell NOS2 abundance and reduce epithelial barrier function at higher concentrations. Intestinal colonization and interaction with R. gnavus are partially regulated by an arginine-NO metabolic pathway, whereby a balanced control by the gut epithelium may restrain R. gnavus growth in healthy individuals. Disruption in this arginine metabolic regulation will contribute to the expansion and blooming of R. gnavus.

Regular physical activity confers health benefits and improves the general quality of life. Recently, alkaline-reduced water (ARW) consumption has garnered increasing attention in the field of sports. ARW effectively inhibits the oxidative stress generated in cells during high-intensity exercises; however, whether it exerts similar effects during exhaustive exercises remains unknown. This study was designed as a randomized, controlled, crossover, double-blind clinical trial with a single intervention of ARW intake (pH 9.5, 10 mL/kg body weight) after intense exercise. The participants were divided into two groups, wherein they consumed either purified water (PW group) or ARW (ARW group). Blood samples were collected before exercise, immediately after exercise, and 15 min after drinking water. The serum levels of oxidative stress markers and fatigue markers were determined. The results showed that ROS (p < 0.01) and NO levels (p < 0.001) were significantly decreased after ARW intake, and the reduction was more pronounced than that in the PW group. Interestingly, the increase in GPx and MDA levels was mediated by ARW intake (both p < 0.05) after exercise. The levels of fatigue markers, such as lactate (p < 0.001), lactate dehydrogenase (p < 0.001), and phosphate (p < 0.001), were significantly reduced in both groups, with ARW intervention showing more decreased markers. The correlation analysis results showed that ARW may help maintain homeostatic conditions for ROS, antioxidant systems, and fatigue markers. These findings indicate that ARW consumption is effective in reducing oxidative stress and fatigue following exhaustive exercise and that ARW could be used as an antioxidant and anti-fatigue supplement after exhaustive physical exercise.

Redox imbalance in intestinal epithelial cells is critical in the early phases of intestinal injury. Dysfunction of the intestinal barrier can result in immunological imbalance and inflammation, thus leading to intestinal syndromes and associated illnesses. Several antioxidants have been discovered to be beneficial in resolving intestinal barrier dysfunction. Of these antioxidants, the effects of alkaline reduced water (ARW) in oxidative stress of intestinal epithelial cells and its immunokine modulation in vitro is unknown. In this study, we utilized ARW-enriched media to investigate its cytoprotective effect against H₂O₂-induced oxidative stress in DLD1 cells. We found that ARW rescued DLD1 from oxidative stress by diluting the influence of H₂O₂ on oxidative stress-activated MAPK signaling and mitochondrial dysfunction. Further, intestinal oxidative stress significantly affects immunokine profiles of Raw 264.7 cells (IL-6, IL-10, MCP, TNF-a, RANTES), which can be reversed by ARW. Collectively, ARW shields intestinal epithelial cells from oxidative stress, reducing the immunological mayhem caused by barrier failure.