In the May 04th issue of The Zealotica Daily, we deciphered 9 articles focusing on: inflammation-related colorectal cancer, enterovirus, covid-19, COVID-19 vaccines, diet-immune interactions, acute diarrhea, and bacteriophage therapy.
<h1 class="pgc-h-arrow-right" data-track="4" >Nature Reviews: How Inflammation Affects the Occurrence and Development of Colorectal Cancer (Review</h1>).
Nature Reviews Immunology——[40.358]
(1) Chronic inflammation induces DNA damage or epigenetic changes by producing reactive oxygen species, which leads to inflammation-related tumorigenesis; (2) inflammatory responses triggered by tumor progression lead to hypoxia-induced cell death and intestinal barrier destruction to play a tumor-promoting role; (3) tumor treatment-induced inflammation promotes tumor progression through DIP released by necrotic cells; (4) intestinal bacteria and their metabolites promote colorectal tumorigenesis by inducing mutations, enhancing tumor-promoting inflammatory responses, and recruiting immunosuppressive cells; (5) Intestinal fungi can also induce mutations by inducing tumor-promoting inflammatory microenvironments or by producing fungal toxins, thereby promoting colorectal tumorigenesis.
【Editor-in-Chief's Comments】
The inflammatory microenvironment plays an important role in the development of colorectal tumors, and the occurrence, progression and prognosis of colorectal cancer are significantly affected by immune cells and stromal cells in the tumor microenvironment. A review article published in Nature Reviews Immunology details the three ways inflammation is involved in regulating the occurrence and development of colorectal cancer: inflammation-related tumorigenesis, tumor-induced inflammation, and treatment-induced inflammation, and discusses the mechanism of action of diet, gut bacteria, and intestinal fungi in inflammation-related colorectal cancer. （@szx）
【Original information】
The inflammatory pathogenesis of colorectal cancer
2021-04-28, doi: 10.1038/s41577-021-00534-x
< h1 class="pgc-h-arrow-right" data-track="12" > the genetic and epigenetic characteristics of IBD-associated colorectal cancer</h1>
Gastroenterology——[17.373]
(1) Tumor tissue and normal colon tissue in 31 IBD-CRC patients were collected; (2) the WNT signaling common to the classical epithelial tumor subtype in IBD-CRC was missing and the mesenchymal matrix was enriched; (3) AXIN2 and RNF43 (negative regulator of WNT signaling) in IBD-CRC were significantly downregulated compared with sCRC, and HNF4A (a negative regulator of WNT-induced epithelial mesenchymal transformation) was reduced; (4) Low methylation enrichment at the HNF4α binding site was detected only in sCRC, while promoter methylation disorders of PIGR and OSMR (involved in mucosal immunity) in IBD-CRC, (5) TP53 5'UTR region mutation enrichment in IBD-CRC, and fewer somatic mutations in APC and KRAS.
IBD is associated with an increased risk of colorectal cancer. IBD-associated colorectal cancer (IBD-CRC) may have different tumorigenesis pathways than sporadic colorectal cancer (sCRC). A new study from Gastroenterology identified genetic and epigenetic traits in tumor tissue in IBD-CRC patients and compared them to sCRC. （@szx）
Genetic and epigenetic characteristics of inflammatory bowel disease associated colorectal cancer
2021-04-26, doi: 10.1053/j.gastro.2021.04.042
<h1 class="pgc-h-arrow-right" data-track="20" >Cell Sub-Journal: Immune Response after Enterovirus Infection</h1>
Cell Host and Microbe——[15.923]
(1) Mice infected with 10 strains of intestinal eukaryotic virus from 6 families were selected, except for CVB3 of the small RNA virus family, other mice were asymptomatic after infection; (2) the intensity and duration of some viral infections depended on intestinal bacteria, and the colonization of various viruses in the intestines of germ-free mice was enhanced; (3) viral infection induced persistent changes in the intestinal immune system (lymphocyte differentiation, IL-22 production, continuous strain-specific response) ;(4) Strain-specific responses are accompanied by common IL-22 and Th1-mediated immune responses; (5) Partial viruses and partial bacteria induce similar intestinal immune responses compared to the mouse gut transcriptome after viral infection and bacterial colonization.
A recent study published in Cell Host and Microbe, using 10 strains of intestinal eukaryotic virus infection in mice from 6 virion families, found that asymptomatic viral infection induces a persistent intestinal immune response, including strain-specific responses and non-strain-specific co-responses (e.g., IL-22 production). In addition, the intestinal transcription of mice after viral infection and bacterial colonization was compared, and the similarities and differences between the intestinal immune response induced by viruses and bacteria were identified. （@szx）
Enteric viruses evoke broad host immune responses resembling those elicited by the bacterial microbiome
2021-04-23, doi: 10.1016/j.chom.2021.03.015
<h1 class="pgc-h-arrow-right" data-track="28" > the role of the enterovirus group and the viral "reservoir" of the intestine (review</h1>).
Good——[19,819]
(1) The enterovirus group plays an important role in maintaining healthy homeostasis of the intestine; (2) the enterovirus group changes in inflammatory intestinal diseases (IBD, IBS, intestinal graft-versus-host disease) and colorectal cancer; (3) the intestine can serve as a reservoir of HIV2, 83%-95% of HIV-infected cells are located in the intestine, and can reach the lymph nodes and blood through immune cell migration; (4) the intestine can also serve as a reservoir of SARS-CoV-2: SARS-CoV-2 can infect intestinal epithelial cells. This leads to the continuous activation of memory B cells and memory T cells; (5) The enterovirus group of the donor should be considered when performing fecal bacteria transplantation.
A review article published in Gut describes changes in the group of enteroviruses in inflammatory bowel diseases and intestinal tumors, and discusses the mechanism of the gut as a reservoir of viruses (HIV and SARS-CoV-2). （@szx）
Gut as viral reservoir: lessons from gut viromes, HIV and COVID-19
2021-04-26, doi: 10.1136/gutjnl-2021-324622
<h1 class="pgc-h-arrow-right" data-track="36" > infliximab may reduce the protective effect of the COVID-19 vaccine in patients with IBD</h1>
(1) 865 patients treated with infliximab and 428 patients with IBD who received vedolizumab were included and the antibody response and serum conversion rate after the COVID-19 vaccine were included; (2) regardless of whether BNT162b2 or ChAdOx1 nCoV-19 was administered, the average concentration of anti-coronavirus antibodies in the infliximab group was significantly lower than that of the vedolizumab group; (3) age ≥ 60 years, immunomodulator use, Crohn's disease (compared to ulcerative colitis and unclassified IBD) and smoking were associated with lower anti-CORONAVIRUS antibody concentrations, while non-white ethnic groups were associated with higher anti-CORONAVIRUS antibody concentrations;
A new study from Gut found that regardless of the COVID-19 vaccine they received— BNT162b2 (co-developed by Pfizer/BioNTech) and ChAdOx1 nCoV-19 (co-developed by Oxford University/AstraZeneca), IBD patients treated with infliximab had significantly lower levels of antibodies against COVID-19 than those treated with vedolizumab. The findings suggest that patients with IBD who received infliximab should receive two doses of the COVID-19 vaccine at the optimal time of vaccination. （@szx）
Infliximab is associated with attenuated immunogenicity to BNT162b2 and ChAdOx1 nCoV-19 SARS-CoV-2 vaccines in patients with IBD
2021-04-26, doi: 10.1136/gutjnl-2021-324789
<h1 class="pgc-h-arrow-right" data-track="44" >SARS-CoV-2 interfere with the intrinsic immune response of the human intestine</h1>
Molecular Systems Biology——[8.991]
(1) Single-cell transcriptome sequencing of SARS-Cov-2-infected human colon and ileal organoids found that only 7-10% of intestinal epithelial cells were infected at 24h and were related to upregulation of IFNλ2-3 expression; (2) Immature intestinal epithelial cell 2 subset was the main target of infected cells by the virus, and ACE2 expression level lacked positive correlation with cell susceptibility; (3) SARS-Cov-2 infection downregulated cell ACE2 expression, inducing pro-inflammatory response, (4) SARS-Cov-2 inhibits the JAK-STAT pathway of infected cells, inhibits their IFN-mediated response, and develops drug resistance to IFN.
An excessive pro-inflammatory immune response contributes to the pathological occurrence of COVID-19. A recent paper by Molecular Systems Biology identified a colon cell subset as the main infectious target of SARS-CoV-2 by sequencing human colon and ileal organoids infected with SARS-CoV-2, and that there was a lack of positive correlation between ACE2 expression and susceptibility to infection. Infected cells induce a strong pro-inflammatory response and expression of IFN, while downregulating ACE2 expression, while IFN acts on bystander cells in a paracrine manner to upregulate the expression of interferon-induced genes. (@Love Choice)
Single‐cell analyses reveal SARS‐CoV‐2 interference with intrinsic immune response in the human gut
2021-04-27, doi: 10.15252/msb.202110232
<h1 class="pgc-h-arrow-right" data-track="52" how > eating too salty affects the function of immune cells</h1>
Traffic——[23.603]
(1) In mouse and human macrophages, extracellular sodium is uptaken into the cell to inhibit mitochondrial respiration; (2) high salt can reduce the activity, oxygen consumption, and ATP production of mitochondrial membrane potential, electron transport chain complex II, independent of the polarization state of macrophages; (3) high-salt treatment can enhance the bactericidal function of M1 macrophages and reduce the migration of CD4+ T cells induced by M2 macrophages; (4) at normal salt concentrations, Disruption of electron transport chains can replicate the transcriptional changes and enhanced bactericidal function of human and mouse monocyte phagocytes induced by high salt; (5) After 14 days/single meal of high salt intake, the plasma sodium of healthy people increased by 2 mM and 2.3 mM, respectively, and the mitochondrial oxygen consumption of monocytes decreased.
High salt intake is one of the main risk factors for death and morbidity. Serum sodium levels are briefly elevated after a meal and can accumulate at sites of inflammation to affect the differentiation and function of congenital and adaptive immune cells. A new study from The Circle found that high salt inhibits mitochondrial respiration in mouse and human monocytes, thereby enhancing the bactericidal function of M1 macrophages while inhibiting the immunosuppressive effects of M2 macrophages. In two trials involving healthy people, high salt intake at 14 days or with a single meal significantly increased sodium levels in plasma and reduced mitochondrial oxygen consumption in monocytes. （@szx）
Salt Transiently Inhibits Mitochondrial Energetics in Mononuclear Phagocytes
2021-04-28, two: 10.1161/CIRCULATIONAHA.120.052788
<h1 class="pgc-h-arrow-right" data-track="60" > domestic team: etiology, epidemiology and clinical features of patients with acute diarrhea in China</h1>
Nature Communications——[12.121]
(1) Data were collected on 152,792 patients with acute diarrhea in China between 2009 and 2018; (2) rotavirus A and norovirus were the most common viral pathogens, followed by adenovirus and astrovirus; (3) diarrhea-causing E. coli and non-typhi Salmonella were the most common bacterial pathogens, followed by Shigella and Vibrio parahaemolyticus; (4) amoebic amoeba was the most common parasitic pathogen, followed by Giardia bluei and Cryptosporidium; (5) more common viral pathogens in patients under 5 years of age. Bacterial pathogens are more common in patients aged 18 to 45 years; (6) Seasonal and geographical factors affect pathogen infection, and the clinical characteristics of infection vary from pathogen to pathogen.
A new study published in Nature Communications by Fang Liqun's team from Anhui Medical University, Wei Liu's team from Peking University, and Li Zhongjie's team from the CdC in Nature Communications identified the proportion of various intestinal pathogen infections (including viruses, parasites, and bacteria) by collecting pathogenic, epidemiological and clinical data from more than 150,000 Patients with Acute Diarrhea in China from 2009 to 2018, and found that the clinical characteristics caused by infections of different pathogens were different. Seasonal and geographical factors have an impact on the type of pathogen infected. The results of this study provide a reference for the formulation of prevention and treatment strategies for acute diarrhea in China. （@szx）
Etiological, epidemiological, and clinical features of acute diarrhea in China
2021-04-29, doi: 10.1038/s41467-021-22551-z
<h1 class="pgc-h-arrow-right" data-track="68" > phage therapy does not affect the patient's gut microbiota</h1>
Microbiome——[11.607]
(1) A patient with Staphylococcus aureus infection received phage therapy (AB-SA01, containing 3 anti-staphylococcal phages) + systemic antibiotic therapy for 4 weeks; (2) stool, skin and saliva samples were collected during the period and analyzed in combination with the microbiota of healthy, antibiotic-treated and ICU populations in the US intestinal program; (3) the patient's intestinal and salivary flora did not change significantly over time, and the Axillary skin samples were significantly reduced; (4) Metabolites exhibit transient and significant changes as a result of phage therapy; (5) genomes of phages used are detected only in the blood,but not in saliva, feces, and skin.
Phage therapy can be used to treat severe bacterial infections, but its effect on the host flora has not been defined. A longitudinal analysis of stool, skin and saliva samples from a patient with Staphylococcus aureus infection who received phage therapy (ARMata Pharmaceuticals AB-SA01) found that there was no significant change in the composition of the fecal and salivary flora during treatment, while staphylococcus genera in the axillary skin decreased significantly, possibly due to a decrease in Staphylococcus aureus due to phage therapy. （@szx）
Assessment of the microbiome during bacteriophage therapy in combination with systemic antibiotics to treat a case of staphylococcal device infection
2021-04-14, doi: 10.1186/s40168-021-01026-9
Thanks to the creators of this issue of the daily: szx, full of joy
Click to read the daily newspaper for the past 10 days:
05-03 | Ketogenic immunotherapy? Target flora for pancreatic cancer? 9 texts at a glance at the progression of digestive cancer
05-02 | Can fasting regulate immunity? 13.4 sub-summary explains the internal logic in detail
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04-30 | Science Today: Is it necessarily good for the intestinal flora to "return to its ancestors"?
04-29 | Gastroenterology is particularly concerned: the use of prebiotic products in the United States has tripled in 20 years
04-28 | "Devil" is also predisposing: Vibrio devil, which makes shrimp less sick and less dead
04-27 | How is "leaky gut" detected? Meticulous and heavy-handed methodology is out
04-26 | Important Review: Is Capsule Endoscopic Bowel Cancer Reliable? 2485 people data revealed the actual effect
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