Lactobacillus helveticus attenuates alcoholic liver injury via regulation of gut microecology in mice.

Previous reports have demonstrated that alcohol consumption significantly reduces the abundance of Lactobacillus in the gut. In this study, we selected five species of the genus Lactobacillus, commonly found in fermented foods, and acknowledged them as safe, edible, and effective in preventing or treating certain diseases, to evaluate their effects on alcoholic liver disease (ALD). By comparing the liver damage indices in each group, we found that the type strain of Lactobacillus helveticus (LH, ATCC 15009) had the most marked alleviating effect on ALD-induced liver injury. Furthermore, experiments combining microbiomics and metabolomics were conducted to explore the mechanisms underlying the hepatoprotective effects of LH. Finally, we discovered that LH mitigated ethanol-induced liver steatosis and inflammation in ALD mice by altering the structure and function of the gut microbiome, increasing intestinal levels of short-chain fatty acids (SCFAs), and enhancing gut barrier integrity. These findings suggest a potential strategy for the clinical management of patients with ALD.

Cellular Senescence in Acute Liver Injury: What Happens to the Young Liver?

Cellular senescence, characterized by irreversible cell cycle arrest, not only exists in age-related physiological states, but has been found to exist in various diseases. It plays a crucial role in both physiological and pathological processes and has become a trending topic in global research in recent years. Acute liver injury (ALI) has a high incidence worldwide, and recent studies have shown that hepatic senescence can be induced following ALI. Therefore, we reviewed the significance of cellular senescence in ALI. To minimize the potential confounding effects of aging on cellular senescence and ALI outcomes, we selected studies involving young individuals to identify the characteristics of senescent cells, the value of cellular senescence in liver repair, its regulation mechanisms in ALI, its potential as a biomarker for ALI, the prospect of treatment, and future research directions.

Longitudinal dynamic single-cell mass cytometry analysis of peripheral blood mononuclear cells in COVID-19 patients within 6 months after viral RNA clearance.

This study investigates the longitudinal dynamic changes in immune cells in COVID-19 patients over an extended period after recovery, as well as the interplay between immune cells and antibodies. Leveraging single-cell mass spectrometry, we selected six COVID-19 patients and four healthy controls, dissecting the evolving landscape within six months post-viral RNA clearance, alongside the levels of anti-spike protein antibodies. The T cell immunophenotype ascertained via single-cell mass spectrometry underwent validation through flow cytometry in 37 samples. Our findings illuminate that CD8 + T cells, gamma-delta (gd) T cells, and NK cells witnessed an increase, in contrast to the reduction observed in monocytes, B cells, and double-negative T (DNT) cells over time. The proportion of monocytes remained significantly elevated in COVID-19 patients compared to controls even after six-month. Subpopulation-wise, an upsurge manifested within various T effector memory subsets, CD45RA + T effector memory, gdT, and NK cells, whereas declines marked the populations of DNT, naive and memory B cells, and classical as well as non-classical monocytes. Noteworthy associations surfaced between DNT, gdT, CD4 + T, NK cells, and the anti-S antibody titer. This study reveals the changes in peripheral blood mononuclear cells of COVID-19 patients within 6 months after viral RNA clearance and sheds light on the interactions between immune cells and antibodies. The findings from this research contribute to a better understanding of immune transformations during the recovery from COVID-19 and offer guidance for protective measures against reinfection in the context of viral variants.

Micro-ecology restoration of colonic inflammation by in-Situ oral delivery of antibody-laden hydrogel microcapsules.

In-situ oral delivery of therapeutic antibodies, like monoclonal antibody, for chronic inflammation treatment is the most convenient approach compared with other administration routes. Moreover, the abundant links between the gut microbiota and colonic inflammation indicate that the synergistic or antagonistic effect of gut microbiota to colonic inflammation. However, the antibody activity would be significantly affected while transferring through the gastrointestinal tract due to hostile conditions. Moreover, these antibodies have short serum half-lives, thus, require to be frequently administered with high doses to be effective, leading to low patient tolerance. Here, we develop a strategy utilizing thin shell hydrogel microcapsule fabricated by microfluidic technique as the oral delivering carrier. By encapsulating antibodies in these microcapsules, antibodies survive in the hostile gastrointestinal environment and rapidly release into the small intestine through oral administration route, achieving the same therapeutic effect as the intravenous injection evaluated by a colonic inflammation disease model. Moreover, the abundance of some intestinal microorganisms as the indication of the improvement of inflammation has remarkably altered after in-situ antibody-laden microcapsules delivery, implying the restoration of micro-ecology of the intestine. These findings prove our microcapsules are exploited as an efficient oral delivery agent for antibodies with programmable function in clinical application.

Dose-Dependent Relationship between Protection of Thioacetamide-Induced Acute Liver Injury and Hyperammonemia and Concentration of Lactobacillus salivarius Li01 in Mice.

Recently, probiotics have been widely used as an adjuvant therapy to cure, prevent, or improve certain diseases. However, no research has been carried out into the dose of probiotics, especially the maximum dose. Therefore, the effective and safe dosage of probiotics needs to be studied. Recently, L. Yang, X. Bian, W. Wu, L. Lv, et al. (Microb Biotechnol 13:1860-1876, 2020, https://doi.org/10.1111/1751-7915.13629) discovered that Lactobacillus salivarius Li01 had a protective effect on thioacetamide-induced acute liver injury and hyperammonemia, and a fixed concentration (3 × 109 CFU/mL) of L. salivarius Li01 was applied in their study. However, the most effective treatment concentration of L. salivarius Li01 remains unknown. Therefore, four concentration gradients of L. salivarius Li01 suspension were prepared for groups of mice to have different levels of bacterial colonization by gavage. Then, acute liver injury and hyperammonemia were induced via thioacetamide administration. By observation and detection, an inverted U-shaped protective effect from L. salivarius Li01 existed in thioacetamide-induced acute liver injury and hyperammonemia. Of note, significant deterioration was confirmed within the group that was orally administered with an excessive concentration of L. salivarius Li01 suspension, and this was attributed to endotoxemia that resulted from compromised immunity, a damaged intestinal barrier, and bacterial translocation. IMPORTANCE This research investigated the relationship between the concentration of Lactobacillus salivarius Li01 and its impact on mice that had a thioacetamide-induced acute liver injury and hyperammonemia. These findings could provide new insights into the effective, proper, and safe use of probiotics.

Incidence and Influencing Factors of New Hepatitis B Infections and Spontaneous Clearance: A Large-Scale, Community-Based Study in China.

Background: Hepatitis B surface antigen (HBsAg) is widely used in hepatitis B screening, and HBsAg seroclearance indicates hepatitis B eradication. Few studies have explored the incidence of and determinants for spontaneous seroclearance using a long-term follow-up cohort study. Our research aimed to examine the incidence of and influencing factors for hepatitis B virus infection and spontaneous clearance of HBsAg from a large-scale cohort in China. Methods: A total of 151,926 resident individuals in Tongxiang underwent HBsAg screening at least thrice in a 7-year period. Serum samples collected at baseline and follow-up examinations were tested for HBsAg. Cox proportional hazard models were used to analyze determinants of HBsAg seroclearance and persistent HBsAg presence. Results: Among the 151,926 participants, new hepatitis B infections occurred in 4,497 participants, yielding an incidence rate of 571.38 per 100,000 person-years. The incidence rate for males was higher than that for females. In the multivariate Cox regression analysis, female gender, alcohol drinking history, hepatitis family history and middle-age group were predictors for persistent positive HBsAg status. Conclusions: The incidence rate of new hepatitis B infections was 571.38 per 100,000 person-years. Male and aged people in this community cohort have a higher infection rate. Alcohol drinking and hepatitis family history were risk factor leading to chronic infection. Female and middle-aged people were prone to persistent positive HBsAg status.