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.

Background and Aims: Acute liver injury (ALI) is a clinical syndrome characterized by rapid loss of liver function, which may progress to life-threatening liver failure. We conducted this meta-analysis to examine the evidence on the effects of probiotics or prebiotics on ALI.Methods and Results: Several databases, including PubMed, EMBASE, and Cochrane Library, were scrutinized from the inception through February 2021 by combining key search terms, yielding 26 eligible studies, which concluded that modulation of gut microbiota significantly decreased aspartate transaminase [standardized mean difference (SMD): −1.51, 95% confidence interval (CI): −2.03 to −1.00], alanine aminotransferase (SMD: −1.42, 95% CI: −1.85 to −0.98), and bilirubin (SMD: −0.91, 95% CI: −1.33 to −0.49). In addition, administration of probiotics or prebiotics also promoted proliferation of Bifidobacterium (SMD: 1.21, 95% CI: −0.18 to 2.60) and inhibited Enterococcus (SMD: −1.00, 95% CI: −1.39 to −0.61), contributing to lower levels of endotoxin (SMD: −2.14, 95% CI: −2.91 to −1.37). Tight junction protein ZO-1 (SMD: 1.95, 95% CI: 0.14 to 3.76) was upregulated after intervention, thereby reducing bacterial translocation to the liver [odds ratio (OR) = 0.23, 95% CI: 0.13–0.44] and mesenteric lymph node (OR = 0.14, 95% CI: 0.08 to 0.26), with decreased tumor necrosis factor-α (SMD: −2.84, 95% CI: −3.76 to −1.93) and interleukin-6 (SMD: −2.62, 95% CI: −4.14 to −1.10). Oxidative stress was also relieved by reducing malondialdehyde (SMD: −1.83, 95% CI: −2.55 to −1.10) while elevating superoxide dismutase (SMD: 1.78, 95% CI: 1.00–2.55) and glutathione (SMD: 1.83, 95% CI: 0.76–2.91).Conclusion: Our findings suggest that probiotics and prebiotics could be a promising therapeutic strategy in ALI and possess a potential for clinical applications.Systematic Review Registration:https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=255888, CRD42021255888.

Background and ObjectiveThere is keen interest in better understanding the impacts of alpha-linolenic acid (ALA), a plant-derived n-3 fatty acid, in ameliorating the development of cancer; however, results of several prospective cohorts present an inconsistent association between ALA intake and the incident colorectal cancer (CRC). We aimed to investigate the summary association of dietary intake and biomarkers of ALA with CRC risk based on the prospective cohorts.MethodsPertinent prospective cohorts were identified in Cochrane Library, PubMed, and EMBASE from inception to February 2022. Study-specific risk ratios (RRs) with 95% confidence intervals (CIs) for comparing the top with the bottom quartiles of ALA levels were combined using a random-effects model. Nonlinear dose-response relationships of ALA levels in diet and blood with CRC risk were assessed using the restricted cubic spline models, respectively.ResultsOver the duration of follow-up with a median of 9.3 years ranging from 1 to 28 years, 12,239 CRC cases occurred among 861,725 participants from 15 cohorts (11 studies on diet and 5 studies on biomarkers including 4 on blood and 1 on adipose tissue). The summary RR was 1.03 (95% CI: 0.97, 1.10; I2: 0.00%) for dietary intake and 0.83 (95% CI: 0.69, 0.99; I2: 0.00%) for biomarker. Each 0.1% increase in the levels of ALA in blood was associated with a 10% reduction in risk of CRC (summary RR: 0.90, 95% CI: 0.80, 0.99; I2: 38.60%), whereas no significant dose-response association was found between dietary intake of ALA and the incident CRC (p for non-linearity = 0.18; p for linearity = 0.24).ConclusionsBlood levels of ALA were inversely and linearly associated with the risk of CRC, which suggested that increased intake of ALA to improve circulating levels was beneficial for CRC prevention.