On July 13, in the "Zealotific Daily", we interpreted 9 articles, focusing on: IBD, clinical endpoints, drug development, new crown, prodromal Alzheimer's disease, PSC, metformin, fecal occult blood, engineered bacteria, drug delivery
Multidisciplinary International Consensus Initiative: How to Design clinical endpoints for IBD
Gastroenterology——[33.883]
(1) For Crohn's disease, symptom relief and endoscopic response are common primary endpoints; (2) Simultaneous use of PRO2 (patient-reported abdominal pain and frequency of bowel movements), Crohn's disease activity index, simplified endoscopic score for Crohn's disease, C-reactive protein, and fecal calcetamin as the core clinical outcome set (COS); (3) For ulcerative colitis, symptoms and endoscopic remission are the main endpoints of the complex; (4) At the same time, the 9-point Mayo clinical score, fecal urgency, Robarts histopathological index or Geboes score, and fecal calcitein were used as COS.
【Editor-in-Chief's Comments】
A multidisciplinary international consensus initiative published at Gastroenterology, with the participation and discussion of 53 experts and 235 patients, made recommendations for the design of clinical endpoints for Crohn's disease and ulcerative colitis. （@aluba）
【Original information】
CORE-IBD: A Multidisciplinary International Consensus Initiative to Develop a Core Outcome Set for Randomized Controlled Trials in Inflammatory Bowel Disease
2022-07-01, doi: 10.1053/j.gastro.2022.06.068
Exploring combination therapies with IBD drugs
Good——[31,793]
(1) For patients with IBD whose disease is uncontrolled, the ACT regimen should be considered; (2) At present, the most commonly used ACT regimen in IBD treatment is vedolizumab + anti-TNF drugs, (3) for elderly patients and debilitated patients, based on safety considerations, the ACT regimen of ustekinumab + vidozuzumab should be preferred; (4) For patients with Crohn's disease (especially in patients with ileal Crohn's disease and intestinal damage), anti-TNF drugs should be considered as the first choice for ACT regimens; (5) For patients with ulcerative colitis, an ACT regimen based on vitolizumab should be considered; (6) For patients with extraintestinal symptoms, anti-TNF drugs or usinumab or JAK inhibitors should be selected.
【Editor-in-Chief's Comments】
Advanced Combination Therapy (ACT) in IBD refers to the combination of two biologics, or one biologic in combination with one small molecule drug. An opinion paper published in Gut discusses in detail how to choose an ACT regimen for different disease types and symptom manifestations in IBD treatment. （@aluba）
【Original information】
The future of drug development for inflammatory bowel disease: the need to ACT (advanced combination treatment)
2022-06-14, doi: 10.1136/gutjnl-2022-327025
The First Affiliated Hospital of Zhejiang University: Changes in respiratory and intestinal flora in patients with new coronary pneumonia
Advanced Science——[17.521]
(1) 66 patients with new coronary pneumonia were included, and the respiratory flora, intestinal flora and PBMCs were analyzed; (2) Compared with non-ICU patients, streptococcus, actinomycetes, kiwi and Bacteroides in the respiratory flora of ICU patients decreased, Enterococcus and Candida increased, Bacteroides in the intestinal flora decreased, and Enterococcus increased; (3) There was a significant positive correlation between the intestinal flora and the relative abundance of respiratory flora; (4) Compared with healthy controls, the prosthetin-related pathways in the PBMC of patients with new coronary pneumonia were adjusted, and the streptococcal genus in the respiratory flora was reduced; (5) Streptococcus and Kiwi bacteria in the respiratory flora can significantly distinguish between ICU patients and non-ICU patients.
【Editor-in-Chief's Comments】
A new study by Chen Yu's team and Zheng Shufa's team at the First Affiliated Hospital of Zhejiang University School of Medicine published a new study in Advanced Science compared and analyzed the respiratory and intestinal flora of 66 patients with 3 stages (hospitalization, progression, and rehabilitation) of COVID-19 patients, and identified the differences in microbiota between ICU patients and non-ICU patients. （@aluba）
【Original information】
Dynamic Alterations in the Respiratory Tract Microbiota of Patients with COVID-19 and its Association with Microbiota in the Gut
2022-07-03, doi: 10.1002/advs.202200956
Xuanwu Hospital: Intestinal dysbacteriosis and intestinal barrier dysfunction in patients with pre-existing Alzheimer's disease whose surgery worsened
Annals of Surgery——[13.787]
(1) 135 elderly people who underwent orthopedic surgery were divided into 3 groups according to preoperative evaluation: 40 controls, 58 subjective cognitive decline (SCD), and 37 amnesiac mild cognitive impairment (aMCI); (2) Before surgery, compared with the control, the short-chain fatty acid producing bacteria in the SCD and aMCI groups decreased, the gram-negative bacteria increased, and the plasma LPS and tight conjugate protein (TJ) levels increased; (3) After surgery, compared with the control, the short-chain fatty acid producing bacteria in the SCD and aMCI groups decreased, the gram-negative bacteria increased, and the plasma claudin level increased; (4) Short-chain fatty acid producing bacteria are negatively correlated with TJ and cytokines; (5) Surgically induced metabolic stress and inflammatory response are associated with changes in intestinal flora.
【Editor-in-Chief's Comments】
The results of a prospective observational cohort study published by Wang Tianlong's team at Xuanwu Hospital in collaboration with foreign researchers in Annals of Surgery found that orthopedic surgery can worsen the existing intestinal flora disorders and intestinal barrier dysfunction in patients with pre-existing Alzheimer's disease (including subjective cognitive decline and amnesia mild cognitive impairment), which is associated with systemic inflammation and may lead to further cognitive decline. （@aluba）
【Original information】
Orthopedic Surgery Causes Gut Microbiome Dysbiosis and Intestinal Barrier Dysfunction in Prodromal Alzheimer’s Disease Patients: A Prospective Observational Cohort Study
2022-06-29, doi: 10.1097/SLA.0000000000005489
Patients with PSC-IBD are at increased risk of atypical and invisible dysplasia
Journal of Crohn's and Colitis——[10.02]
(1) 173 patients with PSC-IBD were enrolled, and 153 dysplasias were detected in 54 patients, of which 35 patients had multiple dysplasias; (2) 61% were atypical dysplasia, 66% were endoscopic invisible dysplasia, and 59% were right/proximal dysplasia; (3) 86 of them were followed up for an average of 55 months, and 37% developed highly dysplasia or colorectal cancer; (4) Patients with PSC-IBD with new organisms have more pancolitis and a longer course of IBD; (5) Compared with patients with non-PSC-IBD with new organisms, the proportion of atypical, invisible and right/proximal dysplasia was higher in patients with PSC-IBD with new organisms.
【Editor-in-Chief's Comments】
Patients with primary sclerosing cholangitis (PSC)-IBD have a higher risk of colorectal neobiology than patients with IBD. The results of a cohort study published in the Journal of Crohn's and Colitis found that about 1 in 3 patients with PSC-IBD had new colorectal organisms and a higher proportion of atypical, invisible, and right/proximal dysplasia. （@aluba）
【Original information】
Increased Risk of Non-Conventional and Invisible Dysplasias in Patients with Primary Sclerosing Cholangitis and Inflammatory Bowel Disease
2022-06-30, doi: 10.1093/ecco-jcc/jjac090
Metformin was not associated with a reduced risk of IBD in older age
Journal of Gastroenterology——[6.772]
(1) Of the 302,863 non-IBD participants from Denmark who had just started taking oral hypoglycemic drugs, 1271 patients with IBD and 12676 controls matched with age, sex and follow-up time were included; (2) Correction of educational level, other immune-mediated inflammatory diseases, DPP-4 inhibitor use, statin use and other factors; (3) There was no significant association between metformin use and IBD risk, Crohn's disease risk, and ulcerative colorectal cancer risk; (4) The cumulative use of metformin and the duration of use of metformin were not significantly associated with the risk of IBD.
【Editor-in-Chief's Comments】
The results of a nested case-control study published in the Journal of Gastroenterology found that metformin use was not significantly associated with IBD risk, including Crohn's disease and ulcerative colitis, among tens of thousands of participants from Denmark. （@aluba）
【Original information】
Metformin use is not associated with reduced risk of older onset inflammatory bowel disease: a Danish nationwide population-based study
2022-07-02, doi: 10.1007/s00535-022-01896-2
A positive stool immunochemical test is associated with an increased risk of rheumatoid arthritis
BMC Medicine——[11.15]
(1) 1,044,955 participants who underwent fecal immunochemical testing (FIT), of which 229,594 were FIT positive and 815,361 were FIT negative; (2) During the average follow-up period of 7.59, a total of 7645 cases of rheumatoid arthritis (RA), 208 cases of systemic lupus erythematosus (SLE) and 101 cases of psoriatic arthritis (PsA) were confirmed; (3) The corrected Cox analysis showed that a positive FIT was associated with an increased risk of RA by 16%, and the Kaplan–Meier analysis showed that a positive FIT was associated with an increased risk of RA by 18%. (4) Positive FIT was not significantly associated with the risk of SLE and PsA.
【Editor-in-Chief's Comments】
A new study published in BMC Medicine, which followed more than 1 million subjects who underwent fecal immunochemistry testing (to check for fecal occult blood) for years, found that a positive result was associated with an increased risk of rheumatoid arthritis rather than systemic lupus erythematosus or psoriatic arthritis. （@aluba）
【Original information】
A positive faecal immunochemical test result and its association with the incidence of rheumatoid arthritis, systemic lupus erythematosus, and psoriatic arthritis: an analysis of one-million national colorectal cancer screening programme results
2022-07-04, doi: 10.1186/s12916-022-02416-y
Nature Sub-Journal: Engineered probiotics regulate intestinal cholelates and inhibit Clostridium difficile infection
Nature Communications——[17.694]
(1) Hydrolase Cb can uncouplate bound bilirates into unbound bilerates, thereby inhibiting the germination and growth of Clostridium difficile; (2) Construct engineered probiotics composed of sensors (sialic acid induction), amplifiers (transcriptional activation gene CadC) and actuators (Cbh) to restore intestinal cholate metabolism and cope with antibiotic-induced dysbacteriosis; (3) In vitro, engineered probiotics can inhibit the germination of Clostridium difficile endospores and the growth of vegetative cells, and reduce the secretion of Clostridium difficile toxins; (4) In vivo mouse models, engineered probiotics inhibit Clostridium difficile infection (CDI) by regulating cholate levels, and improve the prognosis and clinical outcomes of CDI.
【Editor-in-Chief's Comments】
Clostridium difficile infection (CDI) is one of the leading causes of infectious diarrhea. Recently, this article, published in Nature Communications, regulates intestinal cholate metabolism and inhibits CDI by constructing engineered probiotics. This work suggests that bilelate metabolism can be used as a strategy for the treatment of CDI and provides a novel antimicrobial strategy: utilizing the host-pathogen microenvironment as an intervention target to limit CDI. (@Circle)
【Original information】
Engineering probiotics to inhibit Clostridioides difficile infection by dynamic regulation of intestinal metabolism
2022-07-04, doi: 10.1038/s41467-022-31334-z
Nanoparticle Oral Delivery Systems: Progress and Prospects (Review)
Advanced Materials——[32.086]
(1) Oral targeted administration through the intestinal lymphatic system (ILS) can prevent liver first-pass metabolism and increase systemic bioavailability; (2) The granule delivery vector is mainly transported to the lymphatic vessels through intestinal cells and microfolded (M) cells; (3) Lipid-based delivery system includes liposomes, solid lipid NPs, nanoemulsions and lipid-drug conjugates, targeting intestinal cells for transport to lymphatic vessels; (4) Vectors targeting M cells include lipid-based particles, polymer particles and inorganic particles; (5) Yeast microcapsules and their derivatives β dextran, as a new ILS targeting delivery carrier, can improve the defects of poor biocompatibility and insufficient targeting rate, and have potential uses in oral nucleic acid delivery.
【Editor-in-Chief's Comments】
Oral delivery systems are promising in terms of oral vaccines, therapeutic agents to induce mucosal immune responses and the treatment of lymphatic diseases. A review recently published in Advanced Materials introduces the structural and physiological features of the intestinal lymphatic system (ILS), in which intestinal cells and microrefoil (M) cells are the main channels and transport mechanisms for granular delivery carriers from intestinal epithelial cells into lymphatic vessels; A comprehensive overview of the latest advances in particulate carriers and the challenges and opportunities for ILS drug delivery; It also looks forward to the potential use of novel ILS-targeted delivery vectors such as yeast microcapsules and their derived polymerization β-dextran. (@Circle)
【Original information】
Engineering Nano- and Microparticles as Oral Delivery Vehicles to Promote Intestinal Lymphatic Drug Transport
2021-10-01, doi: 10.1002/adma.202104139
Thanks to the creators of this issue of the daily: aluba, Circle, Yuzu cousin
Click to read the daily newspaper for the past 10 days:
07-12 | Wuyang Feng, etc.: Diet therapy improves high blood pressure! An evidence-based diet for antihypertensives that meets Chinese tastes is here
07-11 | Wildfires burn endlessly! Nature reveals the regulatory mechanisms of stem cell sleep in colorectal cancer
07-10 | 1000 people tested: 1 avocado a day, can it improve metabolic health?
07-09 | Zhao Fangqing + Wei Hong and other GUT: a powerful weight loss peptide that inhibits appetite and regulates flora
07-08 | Zhu Shu + Wang Yucai NBE: Cleverly wrapping antibiotics, the effect is greatly increased, and the bacteria are greatly reduced!
07-07 | Nature Today: How Does the Gut Tolerate Food Antigens? A new class of T cells is key
07-06 | Qin Huanlong's team made a breakthrough: "universal" intestinal characteristics + metabolites to help diagnose colorectal cancer
07-05 | Why does anti-PD-1 immunotherapy cause enteritis? Zhong Chao's team's Nature sub-journal reveals new mechanisms
07-04 | JAMA Sub-Journal Review: Improving Cancer Treatment, How Can the Intestinal Flora Exert Its Strength?
07-03 | 9 Wen revisits Chinese and Western diets: disease from the mouth, or eating health?