Efficacy of Gut Microbiome-Targeted Therapies in Modulating Systemic Inflammation and Low-Grade Chronic Inflammatory States in Adults With Metabolic Disorders: A Systematic Review.

Gut microbiome-targeted therapies have shown promise in promoting the outcomes of metabolic inflammation-related disease management. This review aims to assess the effectiveness of microbiome-targeted interventions and pinpoint the most promising therapies for clinical implementation. Following the PRISMA 2020 standards, we searched four main databases: PubMed, EMBASE, Scopus, and the Cochrane Library. We integrated medical subject headings (MeSH) and free-text keywords search pertinent to gut microbiome-targeted interventions, along with related outcomes such as inflammation and insulin resistance. English studies were conducted on primary adults with a metabolic disease diagnosis or deemed a high risk, and were mandated to report at least one outcome pertinent to metabolic health or systemic inflammation. To assess the risk bias, data were extracted, and the Cochrane Risk of Bias (RoB) 2.0 tool was employed. Fifteen studies fulfilled the inclusion criteria. A narrative synthesis was conducted. We found that probiotics significantly enhanced insulin resistance (HOMA-IR), reduced circulating endotoxin levels, decreased visceral fat, BMI, and fat mass, and increased beneficial taxa with obesity-associated bacteria reduction. However, inconsistent outcomes were shown for lipid parameters. Prebiotic therapies showed significant decreases in fasting glucose in overweight people, and insulin levels and HOMA-IR in patients with metabolic syndrome, enhanced anti-inflammatory effects (31% C-reactive protein (CRP) reduction, decreased interleukin (IL)-6, tumor necrosis factor-alpha (TNF)-α, and lipopolysaccharide (LPS) levels), and promoted butyrate-producing bacteria. Synbiotic interventions showed complementary benefits for glucose metabolism and body composition. Fecal microbiota transplantation (FMT) studies indicated improved insulin sensitivity and donor microbiota engraftment in responders. Fiber-rich diet trials markedly improved HbA1c levels in diabetic and prediabetic individuals. In conclusion, prebiotics demonstrated the most consistent metabolic and anti-inflammatory benefits across multiple parameters. Probiotics showed targeted effects on insulin resistance and body composition but inconsistent lipid outcomes. FMT and synbiotics require further investigation to establish clinical efficacy. This evidence supports prebiotics as a priority intervention for metabolic disease management through microbiome modulation.