In the September 07th issue of The Zeitgeon, we deciphered 9 articles focusing on: IBD, parasitic infections, IBD therapeutic drugs, hyaluronic acid, MAIT cells, miRNA, extracellular vesicles.
<h1 class="pgc-h-arrow-right" data-track="4" > chronic infection with Toxoplasma gondii or increased risk of colitis</h1>
PNAS——[11.205]
(1) Toxoplasma gondii chronic infection can worsen DSS-induced mouse colitis; (2) Toxoplasma gondii chronic infection does not change the composition of the intestinal flora of mice, but can damage regenerative stem cells in the colon mucosa and increase the NUMBER of CD4+ T cells and CD8+ T cells recruited by the intestine; (3) Toxoplasma gondii chronic infection can activate Ly6C+ monocytes in the bone marrow and promote the latter to migrate to the intestine and release inflammatory factors (including nitric oxide) to enhance DSS-induced colon damage; (4) In toxoplasma gondii chronically infected mice, knocking out iNOS or removing monocytes using CCR2 monoclonal antibodies relieves symptoms of colitis induced by DSS.
【Editor-in-Chief's Comments】
Many pet lovers may be familiar with Toxoplasma gondii. Previous studies have shown that Toxoplasma gondii infection can lead to intestinal dysbiosis and enteritis, which can be restored during chronic infection, but the long-term effect on the mucosal response has not been clearly defined. A new study from PNAS found that chronic infection with Toxoplasma gondii increased colitis susceptibility in mice and revealed the biological mechanisms behind it. (@Shen Zhixun)
【Original information】
Chronic infection enhances susceptibility to colitis
2021-08-30, doi: 10.1073/pnas.2106730118
<h1 class="pgc-h-arrow-right" data-track="12" > read the parenteral symptoms of IBD (review</h1>).
Gastroenterology——[22.682]
(1) 24% of patients with IBD can develop extraintestinal symptoms (EIM) before the onset of intestinal symptoms, which can affect skeletal muscle, joints, skin, eyes, liver, bile ducts, lungs, pancreas and other parts, including fatigue, pain and other systemic symptoms; (2) genetic risk (including multiple IBD risk gene loci), environmental factors (smoking), immune system activation, molecular simulation of intestinal flora antigens, etc. are the main factors in the pathogenesis of EIM; (3) Most EIMs (peripheral arthritis, etc.) can be resolved after treatment of intestinal inflammation in patients with IBD, but some EIMs (forced spondylitis, etc.) are not related to intestinal inflammation, and the main treatment methods are specific anti-inflammatory therapy and symptomatic therapy.
Inflammatory bowel disease (IBD) is a systemic disorder in which, in addition to intestinal symptoms, extraintestinal symptoms (EIM) can also increase the burden of disease and affect the quality of life of patients. A review article published in Gastroenterology discusses the pathogenesis of EIM and details the epidemiological data, clinical features, and treatment strategies of various types of EIM, including skeletal muscle, skin, eyes, hepatobiliary, and other parts. (@Shen Zhixun)
Extraintestinal Manifestations of Inflammatory Bowel Disease: Current Concepts, Treatment, and Implications for Disease Management
2021-08-03, doi: 10.1053/j.gastro.2021.07.042
< h1 class="pgc-h-arrow-right" data-track="20" > interventions for abdominal pain in patients with ulceration (review</h1>).
Cochrane Database of Systematic Reviews——[9.266]
(1) Summarizing the results of five randomized controlled trials (360 patients with UC), it was impossible to conclude which intervention was effective in treating abdominal pain in patients with UC; (2) the low FODMAP diet did not significantly improve the frequency and degree of abdominal pain compared with the control diet; (3) relaxation training did not significantly improve the frequency and degree of abdominal pain compared with the control group; (4) the therapeutic effect of yoga on abdominal pain could not be confirmed compared with the control group; (5) the intake of kefir did not significantly improve the degree of abdominal pain compared with the control group; (6) Stellate ganglion block therapy significantly improves stomach pain compared to sulfasalazine.
A review article published in the Cochrane Database of Systematic Reviews summarizing data from five randomized controlled trials failed to identify interventions that were effective in relieving abdominal pain in patients with ulcerative colitis (UC). (@Shen Zhixun)
Interventions for the management of abdominal pain in ulcerative colitis
2021-07-22, doi: 10.1002/14651858.CD013589.pub2
<h1 class="pgc-h-arrow-right" data-track="28" > oral α4β7 antagonistic peptides for ulcerative colitis</h1>
(1) In vitro, PTG-100 selectively blocks the binding of α4β7 to MAdCAM-1 (rather than VCAM-1 and ICAM-1) (IC50=1.7nm) ;(2) Oral PTG-100 can be exposed in intestinally relevant lymphoid tissue in mice and binds to α4β7 on CD4+ effector memory T cells at a high level; (3) PTG-100 exposure and target binding in the plasma of healthy volunteers is dose-dependent; (4) In 58 patients with UC who received either placebo or different doses of PCG-100 for 12 weeks, the clinical response rates were 15.8% and 4.8%, the endoscopic response rates were 15.8% and 4.8%, and the histological response rates were 42.9% and 0%, respectively.
PTG-100 is an oral alpha 4β7 antagonistic peptide. A new study from Gastroenterology, reporting the results of a preclinical study, a phase 1 trial, and a phase 2a trial of PTG-100, in 58 patients with ulcerative colitis (UC), oral high-dose (900 mg) PTG-100 for 12 weeks was more effective than placebo to induce clinical response, endoscopic remission, and histological remission. (@Shen Zhixun)
PTG-100, an Oral α4β7 Antagonist Peptide: Preclinical Development and Phase 1 and 2a Studies in Ulcerative Colitis
2021-08-29, doi: 10.1053/j.gastro.2021.08.045
<h1 class="pgc-h-arrow-right" data-track="36" > Subtropical Ecology Institute: use miRNAs to promote probiotic growth and prevent colitis</h1>
Molecular Therapy——[11.454]
(1) In the feces of the recovered DSS-induced colitis mice, the expression of miR-142a-3p was significantly upregulated, and the relative abundance of Lactobacillus reuteri and Lactobacillus yogeri increased; (2) oral miR-142a-3p could alleviate DSS-induced mouse colitis by means of flora dependence; (3) mechanically, miR-142a-3p could promote the growth of Lactobacillus reuteri by targeting the regulation of polA and tag LREU_RS03575; (4) Reuterin, a metabolite of Lactobacillus reuteri, relieves DSS-induced mouse colitis by activating the AMPK pathway.
A new study published in Molecular Therapy by Li Fengna and Zhou Xihong of the Institute of Subtropical Agroecology of the Chinese Academy of Sciences found in a mouse model of DSS-induced colitis that the rehabilitation of colitis was accompanied by changes in the fecal microflora and fecal miRNA, including increased abundance of Lactobacillus reuteri and upregulation of miR-142a-3p expression. Further studies have found that miR-142a-3p can alleviate DSS-induced mouse colitis by promoting the growth of Lactobacillus reuteri. (@Shen Zhixun)
Fecal miR-142a-3p from dextran sulfate sodium-challenge recovered mice prevents colitis by promoting the growth of Lactobacillus reuteri
2021-08-25, doi: 10.1016/j.ymthe.2021.08.025
<h1 class="pgc-h-arrow-right" data-track="44" > target endothelial hyaluronate synthase 3 or treatable IBD</h1>
Matrix Biology——[11.583]
(1) The use of 7-hydroxy-4-methylcoumarin (4-MU) inhibits HA production, which can worsen DSS-induced mouse colitis, manifested by weight loss and increased colon tissue damage; (2) hyaluronic acid synthase 3 (Has3) systemic knockout can play a protective role in DSS-induced mouse colitis, manifested by decreased colitis score and immune cell colon invasion decreased; (3) intestinal epithelial cells and smooth muscle cell specific deletion has3, which has no effect on DSS-induced mouse colitis. May even promote an inflammatory response; (4) Endothelial cell-specific deletion of Has3 may alleviate DSS-induced mouse colitis.
Hyaluronic acid (HA) accumulation is associated with increased colon inflammation and suggests or can be used as a therapeutic target for IBD. A new study published in Matrix Biology found that using drugs to block ha production can worsen DSS-induced colitis in mice. Further studies have found that hyaluronic acid synthase 3 produced by different cells plays a different role in colitis, in which hyaluronate synthase 3 produced by endothelial cells may promote the development of colitis. (@Shen Zhixun)
Endothelial hyaluronan synthase 3 aggravates acute colitis in an experimental model of inflammatory bowel disease
2021-08-28, doi: 10.1016/j.matbio.2021.08.001
<h1 class="pgc-h-arrow-right" data-track="52" > target mucosalally associated constant T cells or treatable IBD</h1>
CMGH Cellular and Molecular Gastroenterology and Hepatology——[9.225]
(1) Activation of MAIT cells can be observed in a mouse model of oxazolone-induced colitis, and knockout of MR1 (missing MAIT cells) alleviates colitis symptoms and improves survival rate in mice; (2) the use of MR1 ligand i6-FP inhibits the activity of MAIT cells, which can reduce the production of the latter pro-inflammatory factors (IFN-γ, TNF-α, etc.) and reduce the pro-inflammatory factors produced by γδ T cells, iNKT cells and CD4+ T cells, thereby alleviating oxazolone-induced mouse colitis; (3) i6-FP does not affect intestinal integrity in normal mice, but reduces pro-inflammatory factor production in circulating MAIT cells in UC patients.
Mucosal-associated constant T (MAIT) cells are innate-like T cells that express the main histocompatibility complex-associated molecule 1 (MR1) and semi-constant TCR. Previous studies have found that infiltration of circulating MAIT cells can be observed in the inflammatory colonic mucosa of patients with ulcerative colitis (UC), and the activation status of the latter is associated with disease activity. The results of a recent study published in CMGH Cellular and Molecular Gastroenterology and Hepatology found that missing MAIT cells or inhibiting MAIT cell activation reduced pro-inflammatory factor production in MAIT cells, thereby alleviating oxazolone-induced mouse colitis. The findings suggest that MAIT cells may be therapeutic targets for IBD. (@Shen Zhixun)
Activated mucosal-associated invariant T cells have a pathogenic role in a murine model of inflammatory bowel disease
2021-08-28, doi: 10.1016/j.jcmgh.2021.08.018
<h1 class="pgc-h-arrow-right" data-track="60" > domestic team: dsDNA in extracellular vesicles activates the STING pathway and promotes Crohn's disease</h1>
Cell Death and Disease——[8.469]
(1) Abnormally elevated levels of dsDNA (including nuclear DNA and mitochondrial DNA) in EVs were positively correlated with disease activity in patients with Crohn's disease, and the STING pathway was activated in the colon mucosa of active Crohn's disease patients; (2) during the active phase of Crohn's disease, the EV secretion of damaged intestinal epithelial cells increased and was internalized by macrophages to induce downstream signals; (3) EVs activated the STING pathway of macrophages in a dsDNA-dependent manner and induced the pro-inflammatory phenotype of macrophages. to promote the development of DSS-induced mouse colitis; (4) The drug GW4869, which blocks EV release, can alleviate DSS-induced mouse colitis by inhibiting the activation of the STING pathway.
A new study by Jian'an Ren and Xiuwen Wu of Jinling Hospital affiliated to Nanjing Medical University and Zhao Yun and his team from BenQ Hospital affiliated to Nanjing Medical University, published in Cell Death and Disease, found that in extracellular vesicles (EVs) in patients with active Crohn's disease, dsDNA levels increased significantly and were positively correlated with disease activity, and the relevant mechanisms were revealed. The results suggest that dsDNA in extracellular vesicles may be used as a diagnostic marker and therapeutic target for Crohn's disease. (@Shen Zhixun)
Extracellular vesicles package dsDNA to aggravate Crohn's disease by activating the STING pathway
2021-08-27, doi: 10.1038/s41419-021-04101-z
< h1 class="pgc-h-arrow-right" data-track="68" > the intestinal fungal group of patients with multiple sclerosis</h1>
EBioMedicine——[8.143]
(1) Case-control studies were conducted in 25 MS patients and 22 healthy controls to analyze stool and blood samples and diet questionnaires at baseline and 6 months later; (2) compared with the control, the α diversity and individual differences between the fungal group of MS patients were significantly increased, and the number of yeast and Aspergillus were increased; (3) the association between the fungal group and the bacterial group, blood immunity and dietary patterns was identified, such as in MS patients, yeast genus was positively associated with blood basophils, negatively associated with regulatory B cells, and Aspergillus was positively associated with activated CD16+ Dendritic cells are positively correlated; (4) Initial treatment with dimethyl fumarate with fungicidal activity did not cause unique changes in the intestinal fungal group in MS patients.
Multiple sclerosis is an autoimmune disease associated with changes in the gut microbiota, but it is unclear how intestinal fungi relate to the disease. A recently published study by EBioMedicine reported for the first time changes in the group of intestinal fungi in patients with multiple sclerosis and their association with gut bacteria, immunity, and diet. （@mildbreeze）
Alterations of the gut mycobiome in patients with MS
2021-08-25, doi: 10.1016/j.ebiom.2021.103557
Thanks to the creators of this issue of the daily: Shen Zhixun, Xu Shuo, Ferryman, LiuYi, Bai Lanmu
Click to read the daily newspaper for the past 10 days:
09-06 | 39 minutes long review detailed explanation: with the microbiota as the center, can it really break through tumor immunity?
09-05 | Nature Food: A small step in diet, a big step in health
09-04 | 4 Articles focus on liver disease: how much is it related to the microflora?
09-03 | Zhai Qixiao and others the latest Microbiome: potential anti-aging bifidobacteria longum
09-02 | Zheng University First Hospital Ren Zhigang and other breakthroughs: oropharyngeal flora may be used to confirm the new crown
09-01 | In August, the 30 most worthwhile gut health articles to read!
08-31 | Cai Jun leads China's RCT to develop NEJM: elderly hypertension must be strengthened to lower blood pressure!
08-30 | Yu Jun's team issued another 22.7 points of gastrointestinal top journal: how high fat bad bacteria promote bowel cancer
08-29 | 16260 Chinese 9 years of tracking: how much carb should I eat to prevent diabetes?
08-28 | How do oral bacteria worsen enteritis? 46 points of review detailed explanation (with a figure to read)