Efficacy of probiotics against dental caries in children: a systematic review and meta-analysis.

Dental caries causes serious consequences and the financial burden of society especially in children with high morbidity rate. Here we carried out a meta-analysis to systematically evaluate the efficacy of probiotics against dental caries in children. Forty-three RCTs were eligible for this meta-analysis after searching the PubMed, Cochrane and Web of Science from the inception through October 2021. Pooled estimates demonstrated that treatment with probiotics significantly reduced noncavitated (dicdas2-6mft) (SMD = -0.18, 95% CI: -0.3 to -0.06, p = 0.002) and cavitated (dicdas5-6mft) carious lesions in children (SMD = -0.32, 95% CI: -0.5 to 0.14, p = 0.0004). Probiotics also reduced prevalence of noncavitated (dicdas2-6mft) carious lesions (RR = 0.8, 95% CI: 0.67 to-0.97, p = 0.02). Salivary Streptococcus mutans was declined after intervention (SMD = -1.17, 95% CI: -1.85 to -0.5, p = 0.0007), while Lactobacillus counts were upregulated (SMD = 1.19, 95% CI: 0.46-1.92, p = 0.001). However, no significant effects in total bacteria counts and salivary pH were observed. Our findings suggest that probiotics especially Lactobacillus could be a promising therapeutic strategy for clinical applications in children dental caries.

Gut microbiota-derived gamma-aminobutyric acid from metformin treatment reduces hepatic ischemia/reperfusion injury through inhibiting ferroptosis.

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 confirmed by the results of fecal microbiota transplantation treatment but showed the elimination of the beneficial effects when gut bacteria were depleted using antibiotics. Detailedly, through 16S rRNA and metagenomic sequencing, we identified that the metformin-reshaped microbiota was characterized by the increase of gamma-aminobutyric acid (GABA) producing bacteria. This increase was further confirmed by the elevation of GABA synthesis key enzymes, glutamic acid decarboxylase and putrescine aminotransferase, in gut microbes of metformin-treated mice and healthy volunteers. Furthermore, the benefit of GABA against HIRI-induced ferroptosis was demonstrated in GABA-treated mice. Collectively, our data indicate that metformin can mitigate HIRI-induced ferroptosis by reshaped gut microbiota, with GABA identified as a key metabolite.

Metformin: update on mechanisms of action on liver diseases.

Substantial attention has been paid to the various effects of metformin on liver diseases; the liver is the targeted organ where metformin exerts its antihyperglycemic properties. In non-alcoholic fatty liver disease (NAFLD), studies have shown that metformin affects the ATP/AMP ratio to activate AMPK, subsequently governing lipid metabolism. The latest research showed that low-dose metformin targets the lysosomal AMPK pathway to decrease hepatic triglyceride levels through the PEN2-ATP6AP1 axis in an AMP-independent manner. Metformin regulates caspase-3, eukaryotic initiation factor-2a (eIF2a), and insulin receptor substrate-1 (IRS-1) in palmitate-exposed HepG2 cells, alleviating endoplasmic reticulum (ER) stress. Recent observations highlighted the critical association with intestinal flora, as confirmed by the finding that metformin decreased the relative abundance of Bacteroides fragilis while increasing Akkermansia muciniphila and Bifidobacterium bifidum. The suppression of intestinal farnesoid X receptor (FXR) and the elevation of short-chain fatty acids resulted in the upregulation of tight junction protein and the alleviation of hepatic inflammation induced by lipopolysaccharide (LPS). Additionally, metformin delayed the progression of cirrhosis by regulating the activation and proliferation of hepatic stellate cells (HSCs) via the TGF-ß1/Smad3 and succinate-GPR91 pathways. In hepatocellular carcinoma (HCC), metformin impeded the cell cycle and enhanced the curative effect of antitumor medications. Moreover, metformin protects against chemical-induced and drug-induced liver injury (DILI) against hepatotoxic drugs. These findings suggest that metformin may have pharmacological efficacy against liver diseases.

Microbial treatment of alcoholic liver disease: A systematic review and meta-analysis.

Background and aims: Alcoholic 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 results: Forty-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-1ß (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. Conclusion: Microbial agents can reverse dysbiosis in ALD, thus significantly interfering with lipid metabolism, relieving inflammatory response and inhibiting oxidative stress to improve liver function.

A Meta-Analysis of Microbial Therapy Against Metabolic Syndrome: Evidence From Randomized Controlled Trials.

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%.