ABSTRACT
Timely liver function recovery (LFR) is crucial for postoperative hepatocellular carcinoma (HCC) patients. Here, we established the significance of LFR on patient long-term survival through retrospective and prospective cohorts and identified a key gut microbe, Bifidobacterium longum, depleted in patients with delayed recovery. Fecal microbiota transfer from HCC patients with delayed recovery to mice similarly impacted recovery time post hepatectomy. However, oral gavage of B. longum improved liver function and repair in these mice. In a clinical trial of HCC patients, orally administering a probiotic bacteria cocktail containing B. longum reduced the rates of delayed recovery, shortened hospital stays, and improved overall 1-year survival. These benefits, attributed to diminished liver inflammation, reduced liver fibrosis, and hepatocyte proliferation, were associated with changes in key metabolic pathways, including 5-hydroxytryptamine, secondary bile acids, and short-chain fatty acids. Our findings propose that gut microbiota modulation can enhance LFR, thereby improving postoperative outcomes for HCC patients.
Subject(s)
Bifidobacterium longum , Carcinoma, Hepatocellular , Liver Neoplasms , Probiotics , Humans , Mice , Animals , Carcinoma, Hepatocellular/surgery , Prospective Studies , Recovery of Function , Retrospective Studies , Liver Neoplasms/surgeryABSTRACT
Depression is the most common mental disorder in the world. Recently, an increasing number of studies have reported alcohol-related depression. However, there is no simple, efficient, and time-saving alcohol-related depression animal model yet. Based on the fact that people with alcohol addiction often have impaired gastrointestinal (GI) tract health like dysbiosis, which serves as a primary factor to augment lipopolysaccharides (LPS), we first developed a murine alcohol-LPS model (mALPS), with oral gavage of LPS in acute alcohol treated mice, and successfully observed depression-like symptoms. We found that acute alcohol treatment damaged the intestinal barrier and caused dysbiosis, which further increased the translocation of LPS and neuroinflammatory responses (TNF-α and IL-1ß) and led to abnormal expression of the depression-related genes, i.e. BDND and IDO, reduced the levels of 5-HT and caused depressive behaviors in mice. Probiotic intervention could improve depressive symptoms without notable adverse effects. Akkermansia muciniphila (AKK), one of the next-generation probiotics, has been widely used for the restoration of the intestinal barrier and reduction of inflammation. Here, we found that AKK significantly ameliorated alcohol-related depressive behaviors in a mALPS model, through enhancing the intestinal barrier and maintaining the homeostasis of the gut microbiota. Furthermore, AKK reduced serum LPS, ameliorated neuroinflammation (TNF-α and IL-1ß), normalized the expression of depression-related genes and increased the 5-HT levels in the hippocampus. Our study suggests that AKK supplements will be a promising therapeutic regime for alcohol-associated depression in the future.
Subject(s)
Akkermansia , Complementary Therapies , Depressive Disorder , Ethanol , Probiotics , Tumor Necrosis Factor-alpha , Animals , Mice , Depressive Disorder/chemically induced , Depressive Disorder/therapy , Dysbiosis/drug therapy , Inflammation/drug therapy , Inflammation/metabolism , Lipopolysaccharides , Serotonin , Tumor Necrosis Factor-alpha/genetics , Tumor Necrosis Factor-alpha/metabolism , Probiotics/therapeutic use , Complementary Therapies/methods , Ethanol/adverse effectsABSTRACT
Along with the excessive use of antibiotics, the emergence and spread of multidrug-resistant bacteria has become a public health problem and a great challenge vis-à-vis the control and treatment of bacterial infections. As the natural predators of bacteria, phages have reattracted researchers' attentions. Phage therapy is regarded as one of the most promising alternative strategies to fight pathogens in the post-antibiotic era. Recently, genetic and chemical engineering methods have been applied in phage modification. Among them, genetic engineering includes the expression of toxin proteins, modification of host recognition receptors, and interference of bacterial phage-resistant pathways. Chemical engineering, meanwhile, involves crosslinking phage coats with antibiotics, antimicrobial peptides, heavy metal ions, and photothermic matters. Those advances greatly expand the host range of phages and increase their bactericidal efficiency, which sheds light on the application of phage therapy in the control of multidrug-resistant pathogens. This review reports on engineered phages through genetic and chemical approaches. Further, we present the obstacles that this novel antimicrobial has incurred.
