No abstract

Background and aims: Metabolic syndrome (MetS), accompanied with significant intestinal dysbiosis, causes a great public health burden to human society. Here, we carried out a meta-analysis to qualify randomized controlled trials (RCTs) and to systematically evaluate the effect of microbial therapy on MetS.Methods and results: Forty-two RCTs were eligible for this meta-analysis after searching the PubMed, Cochrane, and Embase databases. Pooled estimates demonstrated that treatment with microbial therapy significantly reduced the waist circumference (WC) (SMD = −0.26, 95% CI −0.49, −0.03), fasting blood glucose (FBG) (SMD = −0.35, 95% CI −0.52, −0.18), total cholesterol (TC) (SMD = −0.36, 95% CI −0.55, −0.17), low-density lipoprotein cholesterol (LDL-C) (SMD = −0.42, 95% CI −0.61, −0.22), and triacylglycerol (TG)(SMD = −0.38, 95% CI −0.55, −0.20), but increased the high-density lipoprotein cholesterol (HDL-C) (SMD = 0.28, 95% CI.03, 0.52). Sensitivity analysis indicated that after eliminating one study utilizing Bifidobacteriumlactis, results became statistically significant in diastolic blood pressure (DBP) (SMD = −0.24, 95% CI −0.41, −0.07) and in Homeostatic Model Assessment of Insulin Resistance (HOMA-IR) (SMD = −0.28, 95% CI −0.54, −0.03), while the body mass index (BMI) showed significant difference after eliminating one study utilizing oat bran (SMD = −0.16, 95% CI −0.31, −0.01). There was still no significant effect in systolic blood pressure (SBP) and in hemoglobin A1c (HbA1c%).Conclusion: In patients with MetS, the conditioning with microbial therapy notably improves FBG, TC, TG, HDL-C, LDL-C, WC, BMI (except for the study using oat bran), HOMA-IR, and DBP (except for the Study using Bifidobacteriumlactis), however, with no effect in SBP and in HbA1c%.

Background and aimsAlcoholic liver disease (ALD) is characterized by impaired liver function due to chronic alcohol consumption, even fatal in severe cases. We performed a meta-analysis to determine whether microbial agents have therapeutic potential for ALD and elucidate the underlying mechanisms.Methods and resultsForty-one studies were eligible for this meta-analysis after searching the PubMed, Cochrane, and Embase databases. The combined analysis showed that microbial therapy significantly decreased hepatic enzymatic parameters, including alanine transaminase [standardized mean difference (SMD): –2.70, 95% confidence interval (CI): –3.33 to –2.07], aspartate aminotransferase (SMD: –3.37, 95% CI: –4.25 to –2.49), γ-glutamyl transpeptidase (SMD: -2.07, 95% CI: –3.01 to –1.12), and alkaline phosphatase (SMD: –2.12, 95% CI: –3.32 to –0.92). Microbial agents endotoxin to enter the portal circulation and increasing reduced total cholesterol (SMD = -2.75, 95%CI -4.03 to -1.46) and triglycerides (SMD = –2.64, 95% CI: –3.22 to –2.06). Microbial agents increased amounts of the beneficial flora Lactobacillus (SMD: 4.40, 95% CI: 0.97–7.84) and Bifidobacteria (SMD: 3.84, 95% CI: 0.22–7.45), Bacteroidetes (SMD: 2.51, 95% CI: 0.29–4.72) and decreased harmful Proteobacteria (SMD: –4.18, 95% CI: –6.60 to –1.77), protecting the integrity of the intestinal epithelium and relieving endotoxin (SMD: –2.70, 95% CI: -3.52 to –2.17) into the portal vein, thereby reducing the production of inflammatory factors such as tumor necrosis factor-α (SMD: –3.35, 95% CI: –4.31 to –2.38), interleukin-6 (SMD: –4.28, 95% CI: –6.13 to –2.43), and interleukin-1β (SMD: –4.28, 95% CI: –6.37 to –2.19). Oxidative stress was also relieved, as evidenced by decreased malondialdehyde levels (SMD: –4.70, 95% CI: –6.21 to –3.20). Superoxide dismutase (SMD: 2.65, 95% CI: 2.16–3.15) and glutathione levels (SMD: 3.80, 95% CI: 0.95–6.66) were elevated.ConclusionMicrobial agents can reverse dysbiosis in ALD, thus significantly interfering with lipid metabolism, relieving inflammatory response and inhibiting oxidative stress to improve liver function.

Hepatic ischemia/reperfusion injury (HIRI) is a common and inevitable factor leading to poor prognosis in various liver diseases, making the outcomes of current treatments in clinic unsatisfactory. Metformin has been demonstrated to be beneficial to alleviate HIRI in recent studies, however, the underpinning mechanism remains unclear. In this study, we found metformin mitigates HIRI-induced ferroptosis through reshaped gut microbiota in mice, which was verified by the results of fecal microbiota transplantation (FMT) treatment but eliminated by using antibiotics to deplete gut bacteria. Detailedly, 16S rRNA and metagenomic sequencing identified that the metformin-reshaped microbiota was characterized by the increase of gamma-aminobutyric acid (GABA) producing bacteria, which was confirmed by the increase of GABA synthesis key enzymes, glutamic acid decarboxylase (GAD) and putrescine aminotransferase (PAT), in gut microbes of metformin-treated mice and healthy volunteers. Furthermore, the benefit of GABA against HIRI-induced ferroptosis was demonstrated by the results from GABA-treated mice. Collectively, our data indicate that metformin can mitigate HIRI-induced ferroptosis by reshaped gut microbiota, and GABA was identified as a key metabolite.

Hepatic ischemia/reperfusion injury (HIRI) is a common and inevitable factor leading to poor prognosis in various liver diseases, making the outcomes of current treatments in clinic unsatisfactory. Metformin has been demonstrated to be beneficial to alleviate HIRI in recent studies, however, the underpinning mechanism remains unclear. In this study, we found metformin mitigates HIRI-induced ferroptosis through reshaped gut microbiota in mice, which was verified by the results of fecal microbiota transplantation (FMT) treatment but eliminated by using antibiotics to deplete gut bacteria. Detailedly, 16S rRNA and metagenomic sequencing identified that the metformin-reshaped microbiota was characterized by the increase of gamma-aminobutyric acid (GABA) producing bacteria, which was confirmed by the increase of GABA synthesis key enzymes, glutamic acid decarboxylase (GAD) and putrescine aminotransferase (PAT), in gut microbes of metformin-treated mice and healthy volunteers. Furthermore, the benefit of GABA against HIRI-induced ferroptosis was demonstrated by the results from GABA-treated mice. Collectively, our data indicate that metformin can mitigate HIRI-induced ferroptosis by reshaped gut microbiota, and GABA was identified as a key metabolite.