Impact of a Lifestyle Intervention on Gut Microbiome Composition: A Quasi-Controlled Before-and-After Analysis

<b>Background</b>: The human gastrointestinal tract harbors a complex microbiota that plays a vital role in metabolic health. Dysbiosis of the gut microbiome has been linked to metabolic syndrome (MetS), a growing health concern characterized by obesity, hypertension, and dyslipidemia, all of which are strongly associated with insulin resistance and low-grade inflammation. This study aimed to analyze changes in gut microbiome composition and metabolic parameters in individuals with MetS following a 3-month shared medical appointment program driven by a patient-centered agenda with an emphasis on lifestyle pillars of diet, activity, sleep, and stress management. <b>Methods</b>: Thirty-six individuals with MetS were recruited. Of these, 14 completed a structured metabolic health program with facilitated group appointments, including personalized dietary adjustments, increased physical activity, stress management, and clinical monitoring, while 22 served as an untreated group. Fecal samples were collected for full-length 16S rRNA sequencing. Clinical and biochemical parameters, including body weight, blood pressure, HbA1c, triglycerides, and liver enzymes, were assessed. Microbiome data were analyzed for alpha and beta diversity and differential abundance. Correlations between microbial genera and clinical parameters were evaluated using Spearman correlation. <b>Results</b>: Post-intervention, significant improvements were observed in body weight (<i>p</i> = 0.0061), HbA1c (<i>p</i> = 0.033), triglycerides (<i>p</i> = 0.047), AST (<i>p</i> = 0.016), and systolic blood pressure (<i>p</i> = 0.020). Alpha and beta diversity of the gut microbiome showed no significant changes. However, differential abundance analysis revealed increased levels of butyrate-producing and anti-inflammatory genera including Duncaniella, Megasphaera, Pseudoruminococcus, and Oliverpabstia. <b>Conclusions</b>: A 3-month lifestyle intervention in individuals with MetS was associated with marked improvements in metabolic health and beneficial shifts in gut microbiota composition. These findings suggest that even small lifestyle modifications may be a potential therapeutic target for metabolic syndrome management, highlighting the need for personalized approaches in future research.