Diversity and functional prediction of gut microbiota in children with autism spectrum disorder北大核心CSCD

目的分析孤独症谱系障碍(autism spectrum disorder,ASD)儿童肠道菌群结构和多样性,并预测分析菌群的代谢功能。方法采集30例ASD儿童(ASD组)和20例正常发育(typically developing,TD)儿童(TD组)的粪便样本。提取基因组DNA,PCR扩增16S rDNA V4区,使用Illumina NovaSeq6000平台进行高通量测序。分析2组肠道菌群的构成和分布特征,并预测分析菌群的代谢功能。结果ASD组和TD组儿童肠道菌群的α多样性指数(Chao1、Shannon和Simpson)比较差异均无统计学意义(P>0.05)。在门和纲水平,2组儿童肠道菌群的结构差异无统计学意义(P>0.05)。在属水平,ASD组巨单胞菌属、巴恩斯氏菌属、小杆菌属、巨球菌属、瘤胃球菌属扭链群及梭杆菌属的丰度大于TD组(P<0.05)。功能预测分析显示,ASD组肠道菌群的色氨酸降解、谷氨酸降解及丁酸盐生成等代谢功能的丰度低于TD组(P<0.05),而γ-氨基丁酸降解功能的丰度高于TD组(P<0.05)。结论ASD儿童和TD儿童肠道菌群的α多样性无显著差异,但属水平物种构成不同,菌群的代谢功能有差别。     

HMGB1 promotes CXCL12-dependent egress of murine B cells from Peyer's patches in homeostasis

High mobility group box-1 protein (HMGB1) is an alarmin that, once released, promotes inflammatory responses, alone and as a complex with the chemokine CXCL12. Here, we report that the HMGB1–CXCL12 complex plays an essential role also in homeostasis by controlling the migration of B lymphocytes. We show that extracellular HMGB1 is critical for the CXCL12-dependent egress of B cells from the Peyer's patches (PP). This promigratory function of the complex was restricted to the PPs, since HMGB1 was not required for B-cell migratory processes in other locations. Accordingly, we detected higher constitutive levels of the HMGB1–CXCL12 complex in PPs than in other lymphoid organs. HMGB1–CXCL12 in vivo inhibition was associated with a reduced basal IgA production in the gut. Collectively, our results demonstrate a role for the HMGB1–CXCL12 complex in orchestrating B-cell trafficking in homeostasis, and provide a novel target to control lymphocyte migration in mucosal immunity.     

The gut-enthesis axis and the pathogenesis of Spondyloarthritis

Subclinical inflammation is associated with Spondylarthritis (SpA). SpA patients show features of dysbiosis, altered gut barrier function, and local expansion of innate and innate-like cells involved in type 3 immune response. The recirculation of intestinal primed immune cells into the bloodstream and, in some cases, in the joints and the inflamed bone marrow of SpA patients gave the basis of the gut-joint axis theory.In the light of the critical role of enthesis in the pathogenesis of SpA and the identification of mucosal-derived immune cells residing into the normal human enthesis, a gut-enthesis axis is also likely to exist. This work reviews the current knowledge on enthesis-associated innate immune cells' primary involvement in enthesitis development, questions their origin, and critically discusses the clues supporting the existence of a gut-enthesis axis contributing to SpA development.     

One-carbon metabolism markers are associated with cardiometabolic risk factors

Background and aims

Alterations to one-carbon metabolism, especially elevated plasma homocysteine (Hcy), have been suggested to be both a cause and a consequence of the metabolic syndrome (MS). A deeper understanding of the role of other one-carbon metabolites in MS, including s-adenosylmethionine (SAM), s-adenosylhomocysteine (SAH), and the methylation capacity index (SAM:SAH ratio) is required.

Long term effect of gut microbiota transfer on diabetes development

The composition of the gut microbiome represents a very important environmental factor that influences the development of type 1 diabetes (T1D). We have previously shown that MyD88-deficient non-obese diabetic (MyD88−/−NOD) mice, that were protected from T1D development, had a different composition of gut microbiota compared to wild type NOD mice. The aim of our study was to investigate whether this protection could be transferred. We demonstrate that transfer of gut microbiota from diabetes-protected MyD88-deficient NOD mice, reduced insulitis and significantly delayed the onset of diabetes. Gut bacteria from MyD88-deficient mice, administered over a 3-week period, starting at 4 weeks of age, stably altered the family composition of the gut microbiome, with principally Lachnospiraceae and Clostridiaceae increased and Lactobacillaceae decreased. The transferred mice had a higher concentration of IgA and TGFβ in the lumen that was accompanied by an increase in CD8⁺CD103⁺ and CD8αβ T cells in the lamina propria of the large intestine. These data indicate not only that gut bacterial composition can be altered after the neonatal/weaning period, but that the composition of the microbiome affects the mucosal immune system and can delay the development of autoimmune diabetes. This result has important implications for the development of probiotic treatment for T1D.     

Tea polyphenols and their chemopreventive and therapeutic effects on colorectal cancer

Colorectal cancer(CRC),a multifactorial disease,is usually induced and developed through complex mechanisms,including impact of diet and lifestyle,genomic abnormalities,change of signaling pathways,inflammatory response,oxidation stress,dysbiosis,and so on.As natural polyphenolic phytochemicals that exist primarily in tea,tea polyphenols(TPs)have been shown to have many clinical applications,especially as anticancer agents.Most animal studies and epidemiological studies have demonstrated that TPs can prevent and treat CRC.TPs can inhibit the growth and metastasis of CRC by exerting the antiinflammatory,anti-oxidative or pro-oxidative,and pro-apoptotic effects,which are achieved by modulations at multiple levels.Many experiments have demonstrated that TPs can modulate several signaling pathways in cancer cells,including the mitogen-activated protein kinase pathway,phosphatidylinositol-3 kinase/Akt pathway,Wnt/β-catenin pathway,and 67 kDa laminin receptor pathway,to inhibit proliferation and promote cell apoptosis.In addition,novel studies have also suggested that TPs can prevent the growth and metastasis of CRC by modulating the composition of gut microbiota to improve immune system and decrease inflammatory responses.Molecular pathological epidemiology,a novel multidisciplinary investigation,has made great progress on CRC,and the further molecular pathological epidemiology research should be developed in the field of TPs and CRC.This review summarizes the existing in vitro and in vivo animal and human studies and potential mechanisms to examine the effects of tea polyphenols on CRC.     

Possible role of intestinal stem cells in the pathophysiology of irritable bowel syndrome

The pathophysiology of irritable bowel syndrome(IBS) is not completely understood. However, several factors are known to play a role in pathophysiology of IBS such as genetics, diet, gut microbiota, gut endocrine cells,stress and low-grade inflammation. Understanding the pathophysiology of IBS may open the way for new treatment approaches. Low density of intestinal stem cells and low differentiation toward enteroendocrine cells has been reported recently in patients with IBS. These abnormalities are believed to be the cause of the low density of enteroendocrine cells seen in patients with IBS.Enteroendocrine cells regulate gastrointestinal motility, secretion, absorption and visceral sensitivity. Gastrointestinal dysmotility, abnormal absorption/secretion and visceral hypersensitivity are all seen in patients with IBS and haven been attributed to the low density the intestinal enteroendocrine cells in these patients.The present review conducted a literature search in Medline(Pub Med) covering the last ten years until November 2019, where articles in English were included.Articles about the intestinal stem cells and their possible role in the pathophysiology of IBS are discussed in the present review. The present review discusses the assumption that intestinal stem cells play a central role in the pathophysiology of IBS and that the other factors known to contribute to the pathophysiology of IBS such as genetics, diet gut microbiota, stress, and lowgrade inflammation exert their effects through affecting the intestinal stem cells.It reports further the data that support this assumption on genetics, diet, gut microbiota, stress with depletion of glutamine, and inflammation.     

Role of gut microbiota on intestinal barrier function in acute pancreatitis

Acute pancreatitis(AP) is a common gastrointestinal disorder. Approximately15%-20% of patients develop severe AP. Systemic inflammatory response syndrome and multiple organ dysfunction syndrome may be caused by the massive release of inflammatory cytokines in the early stage of severe AP,followed by intestinal dysfunction and pancreatic necrosis in the later stage. A study showed that 59% of AP patients had associated intestinal barrier injury,with increased intestinal mucosal permeability, leading to intestinal bacterial translocation, pancreatic tissue necrosis and infection, and the occurrence of multiple organ dysfunction syndrome. However, the real effect of the gut microbiota and its metabolites on intestinal barrier function in AP remains unclear. This review summarizes the alterations in the intestinal flora and its metabolites during AP development and progression to unveil the mechanism of gut failure in AP.     

Response of gut microbiota to serum metabolome changes in intrahepatic cholestasis of pregnant patients

BACKGROUNDIntrahepatic cholestasis in pregnancy (ICP) is the most common liver disease during pregnancy, and its exact etiology and course of progression are still poorly understood.AIMTo investigate the link between the gut microbiota and serum metabolome in ICP patients.METHODSIn this study, a total of 30 patients were recruited, including 15 patients with ICP (disease group) and 15 healthy pregnant patients (healthy group). The serum nontarget metabolomes from both groups were determined. Amplification of the 16S rRNA V3-V4 region was performed using fecal samples from the disease and healthy groups. By comparing the differences in the microbiota and metabolite compositions between the two groups, the relationship between the gut microbiota and serum metabolites was also investigated.RESULTSThe Kyoto Encyclopedia of Genes and Genomes analysis results showed that the primary bile acid biosynthesis, bile secretion and taurine and hypotaurine metabolism pathways were enriched in the ICP patients compared with the healthy controls. In addition, some pathways related to protein metabolism were also enriched in the ICP patients. The principal coordination analysis results showed that there was a distinct difference in the gut microbiota composition (beta diversity) between the ICP patients and healthy controls. At the phylum level, we observed that the relative abundance of Firmicutes was higher in the healthy group, while Bacteroidetes were enriched in the disease group. At the genus level, most of the bacteria depleted in ICP are able to produce short-chain fatty acids (e.g., Faecalibacterium, Blautia and Eubacterium hallii), while the bacteria enriched in ICP are associated with bile acid metabolism (e.g., Parabacteroides and Bilophila). Our results also showed that specific genera were associated with the serum metabolome.CONCLUSIONOur study showed that the serum metabolome was altered in ICP patients compared to healthy controls, with significant differences in the bile, taurine and hypotaurine metabolite pathways. Alterations in the metabolization of these pathways may lead to disturbances in the gut microbiota, which may further affect the course of progression of ICP.