Background: The Mediterranean diet (MD) could be involved in the regulation of different miRNAs related to metabolic syndrome (MS). Methods: We analyzed the serum level of mir-let7a-5p, mir-21, mir-590, mir-107 and mir-192 in patients with morbid obesity and its association with the MD and MS. Results: There is an association between the adherence to MD and higher serum levels of mir-590. Mir-590 was lower in those patients who consumed >2 commercial pastries/week. Mir-let7a was lower in those who consumed ≥1 sweetened drinks, in those who consumed ≥3 pieces of fruit/day and in those who consumed less red than white meat. A lower mir-590 and mir-let7a, and a higher mir-192 level, were found in patients who met the high-density lipoprotein cholesterol (HDL) criterion of MS. A higher mir-192 was found in those patients who met the triglyceride criterion of MS and in those with type 2 diabetes (T2DM). Conclusions: There is an association between specific serum levels of miRNAs and the amount and kind of food intake related to MD. Mir-590 was positively associated with a healthy metabolic profile and type of diet, while mir-192 was positively associated with a worse metabolic profile. These associations could be suggestive of a possible modulation of these miRNAs by food.

Background: Metabolic dysfunction–associated steatotic liver disease (MASLD) is the most prevalent chronic liver disease worldwide and is strongly linked to obesity, type 2 diabetes, and cardiovascular disease. Growing evidence highlights the role of the gut–liver axis, particularly microbial metabolites such as the short-chain fatty acid (SCFA) butyrate, in MASLD pathophysiology. However, clinical data on butyrate levels and the abundance of butyrate-producing bacteria in MASLD patients remain inconsistent. Objectives: To systematically synthesize human evidence evaluating the associations between butyrate levels and butyrate-producing gut bacteria with MASLD presence and severity, as well as related metabolic comorbidities. Methods: A systematic search was conducted in PubMed and Embase from inception to April 7, 2025, following PRISMA 2020 guidelines (PROSPERO registration CRD420251162439). Eligible studies included observational human research assessing fecal or plasma SCFA concentrations and/or the abundance of butyrate-producing taxa in adults with MASLD and related metabolic disorders. Study quality was appraised using the Newcastle–Ottawa Scale, and results were narratively synthesized due to heterogeneity across methods and outcomes. Results: From 233 records, seven studies met inclusion criteria (2020–2025; n = 1,185). Most were cross-sectional or case–control designs of moderate to high quality (NOS 6–8/9). Individuals with MASLD generally exhibited lower fecal or serum butyrate concentrations and reduced abundance of Faecalibacterium prausnitzii , Eubacterium , and other butyrate-producing bacteria versus controls. These alterations were associated with hepatic steatosis, fibrosis, inflammation, and adverse metabolic profiles - higher BMI, insulin resistance, and dyslipidemia. Geographic and sex-related differences were also reported. Conclusions: This systematic review suggests that reduced butyrate availability and alterations in butyrate-producing gut taxa are associated with MASLD presence and severity and with adverse metabolic traits. However, substantial methodological heterogeneity and the observational design of available studies preclude causal inference. Larger, well-phenotyped, multicentre studies using standardized SCFA quantification, dietary and medication ascertainment, and functional microbiome profiling are needed to validate these findings and clarify their diagnostic and therapeutic implications.

Obesity is frequently accompanied by non-alcoholic fatty liver disease (NAFLD). These two diseases are associated with altered lipid metabolism, in which reverse cholesterol transport (LXRα/ABCA1/ABCG1) and leptin response (leptin receptor (Ob-Rb)/Sam68) are involved. The two pathways were evaluated in peripheral blood mononuclear cells (PBMCs) from 86 patients with morbid obesity (MO) before and six months after Roux-en-Y gastric bypass (RYGB) and 38 non-obese subjects. In the LXRα pathway, LXRα, ABCA1, and ABCG1 mRNA expressions were decreased in MO compared to non-obese subjects (p < 0.001, respectively). Ob-Rb was decreased (p < 0.001), whereas Sam68 was increased (p < 0.001) in MO. RYGB did not change mRNA gene expressions. In the MO group, the LXRα pathway (LXRα/ABCA1/ABCG1) negatively correlated with obesity-related variables (weight, body mass index, and hip), inflammation (C-reactive protein), and liver function (alanine-aminotransferase, alkaline phosphatase, and fatty liver index), and positively with serum albumin. In the Ob-R pathway, Ob-Rb and Sam68 negatively correlated with alanine-aminotransferase and positively with albumin. The alteration of LXRα and Ob-R pathways may play an important role in NAFLD development in MO. It is possible that MO patients may require more than 6 months following RYBGB to normalize gene expression related to reverse cholesterol transport or leptin responsiveness.