Gut microbe and hepatic macrophage polarization in non-alcoholic fatty liver disease.

Non-alcoholic fatty liver disease (NAFLD) is a common chronic hepatic disorder with the potential to progress to hepatic fibrosis, hepatic cirrhosis, and even hepatocellular carcinoma. Activation of hepatic macrophages, important innate immune cells predominantly composed of Kupffer cells, plays a pivotal role in NAFLD initiation and progression. Recent findings have underscored the regulatory role of microbes in both local and distal immune responses, including in the liver, emphasizing their contribution to NAFLD initiation and progression. Key studies have further revealed that gut microbes can penetrate the intestinal mucosa and translocate to the liver, thereby directly influencing hepatic macrophage polarization and NAFLD progression. In this review, we discuss recent evidence regarding the translocation of intestinal microbes into the liver, as well as their impact on hepatic macrophage polarization and associated cellular and molecular signaling pathways. Additionally, we summarize the potential mechanisms by which translocated microbes may activate hepatic macrophages and accelerate NAFLD progression.

Gut microbes in central nervous system development and related disorders.

The association between gut microbiota and central nervous system (CNS) development has garnered significant research attention in recent years. Evidence suggests bidirectional communication between the CNS and gut microbiota through the brain-gut axis. As a long and complex process, CNS development is highly susceptible to both endogenous and exogenous factors. The gut microbiota impacts the CNS by regulating neurogenesis, myelination, glial cell function, synaptic pruning, and blood-brain barrier permeability, with implication in various CNS disorders. This review outlines the relationship between gut microbiota and stages of CNS development (prenatal and postnatal), emphasizing the integral role of gut microbes. Furthermore, the review explores the implications of gut microbiota in neurodevelopmental disorders, such as autism spectrum disorder, Rett syndrome, and Angelman syndrome, offering insights into early detection, prompt intervention, and innovative treatments.

Mucosa-Colonizing Microbiota Correlate With Host Autophagy Signaling in Patients With Inflammatory Bowel Disease.

Both bacteria and autophagy are implicated in inflammatory bowel disease (IBD) pathogenesis. However, how bacteria crosstalk with autophagy signaling remains largely known, especially in intestinal mucosa. This study aimed to profile the internal complex autophagy signaling cascade and their external correlation with these bacteria, and consequently provide a systematic and precise target for future IBD diagnosis and therapy. We found the Ulcerative colitis (UC) patients exhibited more severe dysbiosis than the Crohn's disease (CD) patients, as represented by alpha diversity, community phenotypes, and functional annotation compared with the control population. Meanwhile, CD patients showed greater transcriptional signaling activities of autophagy, endoplasmic reticulum (ER) stress, and bile acid production. Dominant bacteria (e.g., Rhodococcus, Escherichia, Shigella, and Enterococcus) were positively correlated and low-abundance bacteria (e.g., Bacillus, Acidovorax, Acinetobacter, and Stenotrophomonas) were negatively correlated with the autophagy signaling cascade (184 autophagy genes, 52 ER stress genes, and 22 bile acid production genes). Our observations suggested UC patients showed temporary and widespread microbiota turbulence and CD patients showed processive and local autophagy activity during IBD progression. Intestinal mucosa-colonizing bacteria were correlated with the bile/ER stress/autophagy signaling axis in IBD pathogenesis.

Indole alkaloids of Alstonia scholaris (L.) R. Br. alleviated nonalcoholic fatty liver disease in mice fed with high-fat diet.

Alstonia scholaris (L.) R. Br (Apocynaceae) is a well-documented medicinal plant for treating respiratory diseases, liver diseases and diabetes traditionally. The current study aimed to investigate the effects of TA on non-alcoholic fatty liver disease (NAFLD). A NAFLD model was established using mice fed a high-fat diet (HFD) and administered with TA (7.5, 15 and 30 mg/kg) orally for 6 weeks. The biochemical parameters, expressions of lipid metabolism-related genes or proteins were analyzed. Furthermore, histopathological examinations were evaluated with Hematoxylin-Eosin and MASSON staining. TA treatment significantly decreased the bodyweight of HFD mice. The concentrations of low-density lipoprotein (LDL), triglyceride (TG), aspartate aminotransferase (AST) and alanine aminotransferase (ALT) were also decreased significantly in TA-treated mice group, accompanied by an increase in high-density lipoprotein (HDL). Furthermore, TA alleviated hepatic steatosis injury and lipid droplet accumulation of liver tissues. The liver mRNA levels involved in hepatic lipid synthesis such as sterol regulatory element-binding protein 1C (SREBP-1C), regulators of liver X receptor α (LXRα), peroxisome proliferator activated receptor (PPAR)γ, acetyl-CoA carboxylase (ACC1) and stearyl coenzyme A dehydrogenase-1 (SCD1), were markedly decreased, while the expressions involved in the regulation of fatty acid oxidation, PPARα, carnitine palmitoyl transterase 1 (CPT1A), and acyl coenzyme A oxidase 1 (ACOX1) were increased in TA-treated mice. TA might attenuate NAFLD by regulating hepatic lipogenesis and fatty acid oxidation.