The Influence of Early Life Nutrition on Epigenetic Regulatory Mechanisms of the Immune System

The immune system is exquisitely sensitive to environmental changes. Diet constitutes one of the major environmental factors that exerts a profound effect on immune system development and function. Epigenetics is the study of mitotically heritable, yet potentially reversible, molecular modifications to DNA and chromatin without alteration to the underlying DNA sequence. Nutriepigenomics is an emerging discipline examining the role of dietary influences on gene expression. There is increasing evidence that the epigenetic mechanisms that regulate gene expression during immune differentiation are directly affected by dietary factors or indirectly through modifications in gut microbiota induced by different dietary habits. Short-chain fatty acids, in particular butyrate, produced by selected bacteria stains within gut microbiota, are crucial players in this network.     

婴幼儿肠道菌群的影响因素及其在肠道免疫中的作用

婴幼儿肠道菌群自定植起,随着年龄增长,需历经多次改变才能最终形成微生物稳态。本文主要介绍婴幼儿肠道菌群受分娩阶段、喂养方法、饮食结构、生活环境、疾病因素、药物使用后发生的改变,及其在肠道免疫功能形成中发挥的重要作用。     

Shugan granule contributes to the improvement of depression‐like behaviors in chronic restraint stress‐stimulated rats by altering gut microbiota

AimThe investigation aims to evaluate the potential effect of Shugan Granule (SGKL) on the gut, brain, and behaviors in rats exposed to chronic restraint stress (CRS).MethodsThe fecal microbiota and metabolite changes were studied in rats exposed to CRS and treated with SGKL (0.1 mg/kg/day). Depressive behaviors of these rats were determined through an open‐field experiment, forced swimming test, sucrose preference, and weighing. Moreover, LPS‐stimulated microglia and CRS‐stimulated rats were treated with SGKL to investigate the regulation between SGKL and the PI3K/Akt/pathway, which is inhibited by LY294002, a PI3K inhibitor.Results(i) SGKL improved the altered behaviors in CRS‐stimulated rats; (ii) SGKL ameliorated the CRS‐induced neuronal degeneration and tangled nerve fiber and also contributed to the recovery of intestinal barrier injury in these rats; (iii) SGKL inhibited the hippocampus elevations of TNF‐α, IL‐1β, and IL‐6 in response to CRS modeling; (iv) based on the principal coordinates analysis (PCoA), SGKL altered α‐diversity indices and shifted β‐diversity in CRS‐stimulated rats; (v) at the genus level, SGKL decreased the CRS‐enhanced abundance of Bacteroides; (vi) Butyricimonas and Candidatus Arthromitus were enriched in SGKL‐treated rats; (vii) altered gut microbiota and metabolites were correlated with behaviors, inflammation, and PI3K/Akt/mTOR pathway; (viii) SGKL increased the LPS‐decreased phosphorylation of the PI3K/Akt/mTOR pathway in microglia and inhibited the LPS‐induced microglial activation; (ix) PI3K/Akt/mTOR pathway inactivation reversed the SGKL effects in CRS rats.ConclusionSGKL targets the PI3K/Akt/mTOR pathway by altering gut microbiota and metabolites, which ameliorates altered behavior and inflammation in the hippocampus.     

Litchi-Derived Polyphenol Alleviates Liver Steatosis and Gut Dysbiosis in Patients with Non-Alcoholic Fatty Liver Disease: A Randomized Double-Blinded,Placebo-Controlled Study

Preclinical data suggest the role of litchi extract in alleviating non-alcoholic fatty liver disease (NAFLD) by modulating gut microbiota. We aimed at investigating whether oligonol, a litchi-derived polyphenol, could improve liver steatosis and gut dysbiosis in patients with NAFLD. Adults with grade ≥2 steatosis, defined by an MRI proton density fat fraction (MRI-PDFF) of ≥11%, were randomly assigned to receive either oligonol or placebo for 24 weeks. The alteration in the MRI-PDFF and gut microbiota composition assessed by 16S ribosomal RNA sequencing were examined. There were 38 patients enrolled (n = 19 in each group). A significant reduction in the MRI-PDFF between week 0 and week 24 was observed in the oligonol group, while there was a non-significant decrease in the placebo group. A significant improvement in alpha-diversity was demonstrated in both of the groups. The oligonol-induced microbiota changes were characterized by reduced abundance of pathogenic bacteria, including Dorea, Romboutsia, Erysipelotrichaceae UCG-003 and Agathobacter, as well as increased abundance of short-chain fatty acids (SCFAs)-producing bacteria, such as Akkermansia, Lachnospira, Dialister and Faecalibacterium. In summary, this study is the first to provide evidence that supports that oligonol improves steatosis through the modulation of gut bacterial composition. Our results also support the beneficial and complementary role of oligonol in treating NAFLD.     

Gut Microbiota in Psoriasis

Psoriasis is a chronic inflammatory skin disease with autoimmune pathogenic characteristics and is caused by chronic inflammation, which results in uncontrolled keratinocyte growth and defective differentiation. The link between the gut microbiota and immune system regulation opened a novel angle to understand the pathogenesis of many chronic multifactorial diseases, including psoriasis. Current evidence suggests that modulation of the gut microbiota, both through dietary approaches and through supplementation with probiotics and prebiotics, could represent a novel therapeutic approach. The present work aims to highlight the latest scientific evidence regarding the microbiome alterations of psoriatic patients, as well as state of the art insights in terms of microbiome-targeted therapies as promising preventive and therapeutic tools for psoriasis.     

Reciprocal Interaction Between Intestinal Microbiota and Mucosal Lymphocyte in Cynomolgus Monkeys After Alemtuzumab Treatment

It has been known that the gut microbiota plays a central role in shaping normal mucosal immunity, however, little information is available whether the variability of mucosal lymphocytes impacts the commensal flora. Here, we applied a cynomolgus monkey model to characterize the structure and composition of the gut microbiota in response to lymphocyte depletion and to determine their potential association. Molecular profiling of 16S rDNA showed that the intestinal microbiota composition was perturbed after the depletion of mucosal lymphocytes and were recovered following the repopulation. Some specific bacteria from the orders Lactobacillales, Enterobacteriales and Clostridiales, and the genus Prevotella and Faecalibacterium, were primarily responsible for the variations of the gut microbiota after lymphocyte depletion. Interestingly, the species richness of the ileal mucosal microbiota was associated the proportions of TCRαβ⁺ or TCRγδ⁺ T cells (p < 0.01). We demonstrate for the first time the feature of intestinal microbiota composition after lymphocyte depletion and provide novel evidence that the perturbation of gut microbiota is associated with lymphocyte depletion. It may contribute to understand the relationship between gut commensal microbiota and mucosal immune system. Study results provide insight into biological activity of alemtuzumab in intestinal barrier in organ transplantation.     

从骨免疫学到骨微生物学：肠道微生物如何调节骨骼

肠道微生物群被称为人体的第二个基因库,在维持人体平衡中起主要作用。不良饮食习惯、抗生素滥用、病理状态和生活环境改变会对肠道菌群产生负面影响,以引起多种疾病。最新研究发现肠道微生物群与骨质疏松症之间有着密切的联系,同时引入了一个新术语"骨微生物学",该研究领域旨在弥合骨骼生理学、胃肠病学、免疫学和微生物学之间的差距。本文简要介绍了肠道菌群通过免疫系统、新陈代谢和内分泌环境以及其他因素影响骨代谢的潜在机制,通过研究肠道菌群与骨骼健康之间的关系,不仅对于维持骨骼健康和最大程度地减少骨质疏松症很重要,而且对于肠道微生物群是否可作为骨质疏松症新型治疗靶标以及是否可用作骨折预测的生物标志物方面具有重要意义。     

“脑-肠-菌”轴在肠易激综合征发病中的作用

肠易激综合征（IBS）的发病涉及肠道动力障碍、内脏感觉过敏、肠道炎症和免疫反应、精神心理因素等。近年来,脑-肠-菌轴（BGMA）在IBS发病中的作用引起重视,上述的发病因素均可通过神经-免疫-内分泌网络调控方式整合到脑-肠-菌互动框架中进行描述,而且肠道菌群在IBS疾患进程中扮演重要角色。本文从BGMA的组成及其异常在IBS发病中的作用做一综述。     

健康新生儿口腔正常微生物的早期定植研究

目的　观察新生儿口腔微生物的早期定植情况 ,确定健康新生儿口腔正常微生物群的组成以及新生儿口腔中的优势细菌。方法　对 2 2名健康新生儿口腔进行棉拭子取样 ,在需氧、兼性厌氧、厌氧条件下培养 ,培养均采用成品培养基和培养盒 ,培养结果作微生物的形态学及生化鉴定。结果　 90 .9%的刚出生健康新生儿口腔中无菌 ;4 5 .5 %的新生儿出生第 2天即可检出 Streptococcus salivarius(S.salivarius) ,2 7.3%可检出 Streptococ-cus mitis(S.mitis) ,到出生后第 2 8天这两种菌的检出率分别达 86 .4 %和 81.8% ;Candida albicans(C.albicans)在1月龄新生儿口腔中检出率为 2 2 .7% ;母乳喂养与人工喂养的新生儿口腔正常微生物群之间无明显差异 (P>0 .0 5 )。结论　在早期定植于健康新生儿口腔生态区的正常微生物中 ,S.salivarius和 S.mitis为其优势细菌 ,C.albi-cans为优势真菌。不同喂养方式对新生儿口腔优势菌群的组成和数量无明显影响。     

A Comprehensive Analysis of Plasma Cytokines and Metabolites Shows an Association between Galectin-9 and Changes in Peripheral Lymphocyte Subset Percentages Following Coix Seed Consumption

We previously reported that healthy adult males who consumed coix seeds for 1 week demonstrated an increased intestinal abundance of Faecalibacterium prausnitzii and altered peripheral lymphocyte subset percentages. However, the mechanism underlining these effects has not been elucidated. Therefore, cytokines and metabolites in plasma obtained in this study are comprehensively analyzed. A total of 56 cytokines and 52 metabolites in the plasma are quantified. Among them, 14 cytokines and 9 metabolites show significant changes in their levels following coix seed consumption. We examine the relationship between these changes and those in peripheral lymphocyte subset percentages and intestinal abundance of F. prausnitzii, which is also considerably altered following coix seed consumption. The galectin-9 concentration considerably decreased after coix seed consumption, and these changes correlate with those in cytotoxic T cells and pan T cells. Therefore, galectin-9 is possibly involved in the changes in peripheral lymphocyte subset percentages induced by coix seed consumption.