Gut microbiota plays a key role in obesity and non-alcoholic fatty liver disease (NAFLD), so synbiotics could be a therapeutic alternative. We aim to evaluate a nutritional intervention together with the administration of the bacteria Akkermansia muciniphila and the antioxidant quercetin in an in vivo model of early obesity and NAFLD. 21-day-old rats were fed with control or high-fat diet for six weeks. Then, all animals received control diet supplemented with/without quercetin and/or A. muciniphila for three weeks. Gut microbiota, NAFLD-related parameters, circulating bile acids (BAs) and liver gene expression were analyzed. The colonization with A. muciniphila was associated with less body fat, while synbiotic treatment caused a steatosis remission, linked to hepatic lipogenesis modulation. The synbiotic promoted higher abundance of Cyanobacteria and Oscillospira, and lower levels of Actinobacteria, Lactococcus, Lactobacillus and Roseburia. Moreover, it favored elevated unconjugated hydrophilic BAs plasma levels and enhanced hepatic expression of BA synthesis and transport genes. A. muciniphila correlated with circulating BAs and liver lipid and BA metabolism genes, suggesting a role of this bacterium in BA signaling. Beneficial effects of A. muciniphila and quercetin combination are driven by gut microbiota modulation, the shift in BAs and the gut-liver bile flow enhancement.

Obesity is one of the main worldwide public health concerns whose clinical management demands new therapeutic approaches. Bariatric surgery is the most efficient treatment when other therapies have previously failed. Due to the role of gut microbiota in obesity development, the knowledge of the link between bariatric surgery and gut microbiota could elucidate new mechanistic approaches. This study aims to evaluate the long-term effects of bariatric surgery in the faecal metagenome and metabolome of patients with severe obesity. Faecal and blood samples were collected before and four years after the intervention from patients with severe obesity. Biochemical, metagenomic and metabolomic analyses were performed and faecal short-chain fatty acids were measured. Bariatric surgery improved the obesity-related status of patients and significantly reshaped gut microbiota composition. Moreover, this procedure was associated with a specific metabolome profile characterized by a reduction in energetic and amino acid metabolism. Acetate, butyrate and propionate showed a significant reduction with bariatric surgery. Finally, correlation analysis suggested the existence of a long-term compositional and functional gut microbiota profile associated with the intervention. In conclusion, bariatric surgery triggered long-lasting effects on gut microbiota composition and faecal metabolome that could be associated with the remission of obesity.

Gut microbiota (GM) is involved in the maintenance of physiological homeostasis, thus the alteration of its composition and functionality has been associated with many pathologies such as metabolic diseases, and could also be linked with the progressive degenerative process in aging. Nowadays, life expectancy is continuously rising, so the number of elder people and the consequent related pathologies demand new strategies to achieve healthy aging. Besides, actual lifestyle patterns make metabolic diseases a global epidemic with increasing trends, responsible for a large mortality and morbidity in adulthood and also compromising the health status of later stages of life. Metabolic diseases and aging share a profile of low-grade inflammation and innate immunity activation, which may have disturbances of GM composition as the leading mechanism. Thus, GM emerges as a therapeutic target with a double impact in the elderly, counteracting both aging itself and the frequent metabolic diseases in this population. This review summarizes the role and compositional changes of the GM in aging and its modulation through nutritional interventions and physical exercise as a strategy to counteract the aging process and the related metabolic diseases.

Several hepatic disorders are influenced by gut microbiota, but its role in idiosyncratic drug-induced liver injury (iDILI), whose main causative agent is amoxicillin–clavulanate, remains unknown. This pioneering study aims to unravel particular patterns of gut microbiota composition and associated metabolites in iDILI and iDILI patients by amoxicillin–clavulanate (iDILI-AC). Thus, serum and fecal samples from 46 patients were divided into three study groups: healthy controls (n = 10), non-iDILI acute hepatitis (n = 12) and iDILI patients (n = 24). To evaluate the amoxicillin–clavulanate effect, iDILI patients were separated into two subgroups: iDILI non-caused by amoxicillin–clavulanate (iDILI-nonAC) (n = 18) and iDILI-AC patients (n = 6). Gut microbiota composition and fecal metabolome plus serum and fecal bile acid (BA) analyses were performed, along with correlation analyses. iDILI patients presented a particular microbiome profile associated with reduced fecal secondary BAs and fecal metabolites linked to lower inflammation, such as dodecanedioic acid and pyridoxamine. Moreover, certain taxa like Barnesiella, Clostridia UCG-014 and Eubacterium spp. correlated with significant metabolites and BAs. Additionally, comparisons between iDILI-nonAC and iDILI-AC groups unraveled unique features associated with iDILI when caused by amoxicillin–clavulanate. In conclusion, specific gut microbiota profiles in iDILI and iDILI-AC patients were associated with particular metabolic and BA status, which could affect disease onset and progression.

Metabolic dysfunction-associated steatotic liver disease (MASLD) is the most common cause of chronic liver disease worldwide. Fibrosis is the main prognostic factor and the last reversible stage before cirrhosis, yet therapeutic options remain limited. Given the strong contribution of gut dysbiosis to MASLD progression, strategies targeting the gut microbiota are of growing interest. This study aims to evaluate the effect of melatonin, a well-known antioxidant, anti-inflammatory and antifibrotic compound, and Akkermansia muciniphila, a next-generation probiotic, on a MASLD-associated liver fibrosis model. Eight-week-old C57BL/6J mice were fed with control or Western diet supplemented with fructose and intraperitoneal CCl₄ to induce liver fibrosis. After eight weeks, animals received either no intervention, melatonin, A. muciniphila, or both for four weeks. Serum biochemistry, liver histology and gut and liver gene expression were evaluated and multi-omic analyses were performed, including gut microbiota profiling and faecal metabolomics. Statistical analyses assessed intergroup differences and correlations across datasets. Both interventions partially restored gut microbiota composition and functionality and modulated hepatic and intestinal gene expression. Melatonin and A. muciniphila exerted protective effects against MASLD-associated fibrosis, which supports their potential as adjunctive therapeutic strategies to mitigate liver injury through modulation of the gut–liver axis.

Metabolic dysfunction-associated steatotic liver disease (MASLD) is the most common cause of chronic liver disease worldwide. Fibrosis is the main prognostic factor and the last reversible stage before cirrhosis, yet therapeutic options remain limited. Given the strong contribution of gut dysbiosis to MASLD progression, strategies targeting the gut microbiota are of growing interest. This study aims to evaluate the effect of melatonin, a well-known antioxidant, anti-inflammatory and antifibrotic compound, and Akkermansia muciniphila, a next-generation probiotic, on an MASLD-associated liver fibrosis model. Eight-week-old C57BL/6J mice were fed a control or Western diet supplemented with fructose and intraperitoneal CCl₄ to induce liver fibrosis. After eight weeks, the animals received either no intervention, melatonin, A. muciniphila, or both for four weeks. Serum biochemistry, liver histology and gut and liver gene expression were evaluated and multi-omic analyses were performed, including gut microbiota profiling and faecal metabolomics. Statistical analyses assessed intergroup differences and correlations across datasets. Both interventions partially restored gut microbiota composition and functionality and modulated hepatic and intestinal gene expression. Melatonin and A. muciniphila exerted protective effects against MASLD-associated fibrosis, which supports their potential as adjunctive therapeutic strategies to mitigate liver injury through modulation of the gut–liver axis.