Topics in this issue: Microbial Ecology, Immunotherapy, Childhood Obesity, Metabolic Syndrome, Type 1 Diabetes, Circadian Rhythms, Medical Devices, Biomaterials, Enteric Nervous System, Intestinal Development, Enterome, Bristol-Myers Squibb, China Resources Shuanghe, Hanyu Pharmaceuticals, Boston Scientific
The daily newspaper was published by R. AI-assisted creation generation, manual review and proofreading.
Science: Bacteriophage-germ "arms race" in the gut of cholera patients
Science——[56.9]
(1) Metagenomic analysis of the feces of patients with diarrhea in Bangladesh, quantitative analysis of Vibrio cholerae (prey) and its virulent bacteriophage (ICP1, predator), and the inclusion of antibiotic exposure factors to study the evolution of phage-bacterial interaction and its impact on patients' disease;(2) The ratio of ICP1 to Vc (ICP1:Vc) can be used as a marker of disease severity in patients, and patients with high ICP1:Vc have mild dehydration symptoms, ICP1: Symptoms are severe when Vc is low, suggesting that ICP1 inhibits Vc and alleviates disease in patients;(3) the antibiotic azithromycin inhibits Vc and ICP1 in a dose-dependent manner, whereas ciprofloxacin does not have this inhibitory effect and may be related to the resistance gene encoded by Vc;(4) phage predation is "effective" in the absence of Vc defense (i.e., the integrative junction element (ICE) encoding the antiphage gene is not detectable in the patient, ICP1: (5) In the presence of anti-phage defense (especially in the presence of the Ind5 ICE variant), phage predation is "ineffective", and ICP1:Vc is low, at which point genetic diversity increases to bypass Vc's anti-phage defense;(6) The study reveals the bacteria-phage coevolutionary "arms race" in cholera patients , this co-evolution should be taken into account when performing phage-based therapies and diagnostics.
【Original Information】
Phage predation, disease severity, and pathogen genetic diversity in cholera patients
2024-04-19, doi: 10.1126/science.adj3166
The first RCT of microbiota marker stratification: modulation of the effect of gut microbiota on immunotherapy for melanoma
Cancer Discovery——[28.2]
(1) This study is the first randomized, placebo-controlled, Phase 1b microbiome modulation clinical trial using biomarker stratification to explore ways to improve the response to immune checkpoint inhibitors (ICBs) in melanoma patients by modulating the gut microbiota; Fourteen melanoma patients were recruited and divided into two groups with high and low abundance of Ruminococcaceae according to the characteristics of intestinal flora, and randomly assigned to SER-401 group (vancomycin pretreatment→ SER-401 (oral preparation enriched with firmicutes spores) →nivolumab (anti-PD-1) + SER-401), or placebo group (placebo antibiotic→placebo microbiota modulation (PMM) →nivolumab+PMM) ;(3) Treatment with SER-401 in combination with nivolumab was safe, with objective response rates of 25% and 67% in the SER-401 and placebo groups, respectively, but statistical power was insufficient due to under-recruitment during the COVID-19 pandemic;(4) Vancomycin pretreatment disrupts the gut microbiota and impairs immune function, and does not fully recover by the time of ICB administration (especially in patients with high abundance of Ruminococcaceae) ;(5) Future design of such trials should take into account the antibiotic conditioning and dose of the intervention in the protocol.
【Original Information】
Randomized Placebo-Controlled, Biomarker-Stratified Phase Ib Microbiome Modulation in Melanoma: Impact of Antibiotic Preconditioning on Microbiome and Immunity
2024-04-04, Doi: 10.1158/2159-8290.CD-24-00666
Domestic team: Prevalella intestinal may cause childhood obesity
Gut Microbes——[12.2]
(1) Wu Shusong's team from Hunan Agricultural University and Peng Lijun's team from Hunan Children's Hospital revealed for the first time a significant positive correlation between Prevotella copri (P.c) in the intestinal microbiota and childhood obesity, and explored the effect of P.c on obesity through experiments;(2) Transplantation of P.c could significantly increase the serum fasting blood glucose, insulin and interleukin-1β (IL-1β) levels in high-fat diet-induced obese mice, but had no effect on normal mice;(3) P.c can reduce the relative abundance of Akk bacteria in the intestinal microbiota of mice;(4) At the same time, P.c can also increase the levels of primary bile acid and ursodeoxycholic acid (UDCA) in high-fat diet mice;(5) The study suggests that the effect of P.c on childhood obesity may be related to the regulation of insulin levels, intestinal microbiota and bile acid metabolism.
【Original Information】
Effects of Prevotella copri on insulin, gut microbiota and bile acids
2024-04-16 , Yogurt: 10.1080/19490976.2024.2340487
HELIUS STUDY NEW FINDINGS: METABOLIC SYNDROME OF DIFFERENT ETHNICITIES IS ASSOCIATED WITH GUT MICROBIOTA
Genome Medicine——[12.3]
(1) This study revealed racial differences in metabolic syndrome (MetS) and whether there is a racially independent or ethnically specific association between gut microbiota composition and the components of MetS;(2) In 16,209 untreated participants of six races, the prevalence of MetS itself, its individual components, and their combinations was found to vary between ethnicities and are often related to sex;(3) Indicators of gut microbiota composition (α-diversity, Individual ASVs and RCM Nutrition Network) were inter-ethnic, and if racial independence effects were assumed, most of these measures were associated with better MetS outcomes;(4) α diversity and the association of RCM Nutrition Networks with MetS outcomes were race-dependent, with higher diversity among the Dutch associated with better MetS outcomes, and sometimes in other ethnic groups, and hypertension in Ghanaians;(5) There is heterogeneity of MetS characteristics among different ethnic groups, and there is a race-independent or race-specific association between gut microbiota and MetS, and the treatment of metabolic syndrome and its relationship with gut microbiota should be determined according to local conditions in multi-ethnic populations.
【Original Information】
Ethnic variations in metabolic syndrome components and their associations with the gut microbiota: the HELIUS study
2024-03-20, doi: 10.1186/s13073-024-01295-7
National team: mNFE can be used to predict the state before the onset of type 1 diabetes
Gut Microbes——[12.2]
(1) Chen Luonan from the University of the Chinese Academy of Sciences and Li Peiluan from Henan University of Science and Technology published their latest research in Gut microbes as a joint communication, proposing a new method microbiome network flow entropy (mNFE) for the detection of type 1 diabetes mellitus (T1D) pre-critical state and dynamic network biomarkers (DNBs);(2) The mNFE method has been verified by numerical simulation at different noise levels, which proves its robustness; (3) The application of practical datasets shows that mNFE can successfully identify the critical state of T1D and discover DNBs at different taxonomic levels;(4) identify some high-frequency species closely related to the clinical characteristics of autoantibodies, as well as non-differential "dark species" that play an important role in the progression of T1D;(5) mNFE provides a new research approach for the early diagnosis and preventive medicine of T1D, and also provides the possibility for the preventive treatment of other diseases.
【Original Information】
mNFE: microbiome network flow entropy for detecting pre-disease states of type 1 diabetes
2024-03-21 , Yogurt: 10.1080/19490976.2024.2327349
Cell: Circadian rhythm of tryptophan metabolism driven by gut microbiota under acute stress
Cell Reports——[8.8]
(1) This study revealed the circadian changes of intestinal microbiota by affecting tryptophan metabolism to regulate intestinal stress, indicating that microbiota is essential for maintaining the normal circadian rhythm of intestinal barrier and host tryptophan metabolism;(2) acute stress increases intestinal permeability in vivo and changes the concentration of tryptophan metabolites in host and microorganisms;(3) tryptophan metabolism in bacteria and microorganisms exhibits circadian rhythmic behavior;(4) Acute stress affects the degradation of host tryptophan in the gut in a region-dependent manner, and a stressor of 15 minutes is sufficient to alter cecal tryptophan metabolism and increase in vivo permeability in bacteria-colonized mice, independent of microbial status;(5) The rhythmic nature of colonic Ido1 and Tph1 depends on the presence of microflora at the transcriptional level, and any change in microflora disrupts colonic serotonin production, resulting in increased ileal serotonin synthesis.
【Original Information】
The microbiota drives diurnal rhythms in tryptophan metabolism in the stressed gut
2024-04-11 , doi: 10.1016/j.celrep.2024.114079
Oral self-energy stimulators may be used to treat obesity and metabolic diseases
Advanced Materials——[29.4]
(1) In this study, a novel oral self-powered electrical stimulator was developed for the treatment of obesity and metabolic disorders;(2) The electrical stimulator consists of piezoelectric barium titanate (BTO) particles combined with capsaicin (Cap) to activate the vagus nerve;(3) Diet-induced obesity (DIO) mice were ingested, and BTO@Cap particles were able to specifically target Cap-sensitive sensory nerve endings in the gastric mucosa;(4) The particles were stimulated by gastric peristalsis to generate electrical signals, which were transmitted to the hypothalamus through the gut-brain axis, enhancing the brain's satiety signal, reducing food intake, and promoting energy metabolism with little toxicity;(5) Compared with the control group, DIO mice treated with BTO@Cap pellets/day for three weeks had significant weight loss and maintained normal motor activity;(6) The treatment also alleviated a variety of metabolic changes associated with obesity, showing potential for the treatment of other neurological diseases in the brain.
【Original Information】
Orally Ingested Self-Powered Stimulators for Targeted Gut-Brain Axis Electrostimulation to Treat Obesity and Metabolic Disorders
2024-04-09 , doi: 10.1002/adma.202310351
Synthetic colonic mucus may be used as a mucus layer organoid module
Advanced Functional Materials——[19]
(1) Supramolecular gel FAMS was formed based on the self-assembly of the unnatural amino acid Fmoc-pentafluoro-L-phenylalanine (Fmoc-FF) at the interface between perfluoronaphthalene and normal saline solution by screening surfactant libraries, and the fiber network could be transformed into an aqueous structure after incubation at 37°C, which can be used to simulate colonic mucus; FAMS can be modified by GFP or BSA proteins, and mucins BSM and PGM can also achieve non-covalent modification of their surfaces without damaging the gel structure;(3) FAMS exhibits a dynamic viscosity comparable to that of human colon mucus, which changes with the change of environmental pH, and is close to the natural mucus characteristics;(4) Robust colonization and growth on FAMS were achieved using Escherichia coli, Lactobacillus acidophilus, and Lactobacillus rhamnosus;(5) Based on the FAMS carried on Caco2 cells, the rapid adhesion of cells to FAMS was found to be inoculated with E. coli, and this Caco2-FAMS-microbial mixture was found to form a tightly integrated system, similar to the distribution of natural mucus layers.
【Original Information】
Synthetic Colonic Mucus Enables the Development of Modular Microbiome Organoids
2024-03-13 , doi: 10.1002/adfm.202402514
Cell sub-journal of the domestic team: key molecular mechanisms of enteric nervous system development in mouse embryos
Developmental Cell——[11.8]
(1) During the development of the enteric nervous system (ENS), pioneer wavefront intestinal nerve crest cells (ENCCs) initiate intestinal colonization, and Jiexiong Feng from Huazhong University of Science and Technology and Zhihua Liu from Hubei University and their team revealed the spatiotemporal dynamics and molecular characteristics of ENCCs in mouse embryos through single-cell RNA sequencing and spatial transcriptomics, providing new insights for understanding the development of the enteric nervous system (ENS); (3) The key signaling pathways, including ephrin-Eph, Wnt-Frizzled, and Sema3a-Nrp1 pathways, were revealed on which wavefront ENCCs interact with surrounding cells, and the disruption of these pathways was observed in the intestinal tissues of patients with Hirschsprung's disease, which was associated with ENS malformations; When wavefront ENCCs reach specific intestinal regions, they can cause transcriptional changes in specific regions and cell types of surrounding intestinal tissue, suggesting that they play a role in shaping the intestinal microenvironment.
【Original Information】
Identification of signaling pathways that specify a subset of migrating enteric neural crest cells at the wavefront in mouse embryos
2024-04-15 , doi: 10.1016/j.devcel.2024.03.034
Cell子刊:Mayo/CG11318调控果蝇中肠发育
Cell Reports——[8.8]
(1) Adhesion G protein-coupled receptors (aGPCRs) are a large class of cell surface molecules with multiple functions in organ development, and this study found that CG11318/mayo in aGPCR is specifically expressed in the gastrointestinal and anal regions, which can control potassium homeostasis and regulate midgut development;(2) CG11318 mayo encoding aGPCR, and the absence of mayo in the gut leads to hyperkalemia and rapid heartbeat phenotype;(3) Hyperkalemia in Drosophila can be simulated by increasing potassium concentration, while inhibition of potassium channels with drugs can restore potassium levels in Drosophila mayoKO mutants;(4) Mayo mainly controls midgut size, hyperkalemia, and cardiac acceleration phenotype through intestinal cell proliferation, rather than due to cellular autonomy;(5) This finding reveals CG11318/mayo as a homeostatic regulator of intestinal development, providing a new perspective for understanding the function of aGPCR in organ development.
【Original Information】
The adhesion G-protein-coupled receptor mayo/CG11318 controls midgut development in Drosophila
2024-01-04 , doi: 10.1016/j.celrep.2023.113640
Enterome完成管线药物EO2401 ROSALIE研究
(1) On April 17, Enterome announced that it has completed clinical data collection for the EO2401 ROSALIE study of its pipeline under investigation, (2) the study is designed to evaluate the efficacy and safety of EO2401 in combination with nivolumab in patients with recurrent glioblastoma with or without anti-VEGF therapy, (3) EO2401 is a number of microbial-derived antigenic peptides that mimic antigens expressed by tumor cells, and (4) In the ROSALIE trial, clinical efficacy was observed in approximately one-third of patients in the EO2401 group, compared to only one-tenth of patients with standard treatment, and the results of this study are expected to be published by the end of 2024.
【Original Information】
Enterome Announces Successful Completion of Phase 2 ROSALIE Study of EO2401 in Recurrent Glioblastoma
2024-04-17 , GlobeNewswire
Bristol-Myers Squibb's Opdivo + Yervoy combination has filed a new indication in China
(1) On April 18, Bristol-Myers Squibb (BMS) filed a new indication in China for the combination of Opdivo (nivolumab) and Yervoy (ipilimumab), (2) the combination is intended for the first-line treatment of unresectable or metastatic microsatellite instability (MSI-H) or mismatch repair deficient (dMMR) colorectal cancer (CRC) ;(3) Previously, a Phase 3 CheckMate-8HW study showed a 79% reduction in the combination compared to chemotherapy (4) The new indication of the combination was proposed for priority review by the Center for Drug Evaluation (CDE) of the National Medical Products Administration (NMPA) on March 27.
【Original Information】
Opdivo + Yervoy Combination Declares New Indication in China for First-Line Treatment of Colorectal Cancer
2024-04-18 , 医药魔方Info
CR Shuanghe Semaglutide Injection was approved for clinical trial
(1) On April 15, China Resources Shuanghe Pharmaceutical Co., Ltd. announced that it had obtained the "Drug Clinical Trial Approval Notice" for semaglutide injection issued by the National Medical Products Administration ;(2) Semaglutide injection is suitable for blood sugar control and cardiovascular disease reduction in adult patients with type 2 diabetes; (3) The drug was developed by Novo Nordisk and has been marketed in the United States, the European Union and other places, with global sales of US$20.1 billion (about RMB 145.49 billion) in 2022 ;(4) At present, there is no similar drug on the market in China, and CR Shuanghe is one of the 14 companies that have been approved for clinical trials.
【Original Information】
China Resources Shuanghe Pharmaceutical Co., Ltd. Announcement on Semaglutide Injection Obtaining the Notice of Approval for Drug Clinical Trials
2024-04-16 , 华润双鹤
Semaglutide injection of Hanyu Pharmaceutical Co., Ltd. was approved for clinical trial
(1) On April 16, Hanyu Pharmaceuticals announced that its semaglutide injection had obtained clinical approval issued by the State Food and Drug Administration;(2) the application indication for semaglutide injection was weight management, and it reduced blood sugar levels and the risk of major cardiovascular events (such as heart attack or stroke) in patients with type 2 diabetes; (3) semaglutide is a GLP-1 receptor agonist that works by increasing insulin release, decreasing glucagon release, delaying gastric emptying, and reducing appetite;(4) Semaglutide is currently protected by the original patent, only Novo Nordisk is listed, and many domestic companies have deployed the drug, and there is uncertainty in the future market competition.
【Original Information】
Hanyu Pharmaceutical: Announcement on semaglutide injection obtaining the notice of approval for clinical trials
2024-04-18 , Oriental Fortune Network
The FDA is urgently recalling Boston Scientific's hemostatic product, Obsidio Embolic
(1) On April 17, the U.S. FDA notified Boston Scientific of of a recall of its lower gastrointestinal hemostatic product, Obsidio Embolic, with the recall being classified as "most severe";(2) the device may increase the risk of intestinal ischemia when treating gastrointestinal bleeding, (3) the FDA said it had reported 11 related incidents, including seven injuries and two deaths;(4) Boston Scientific does not recommend that doctors use the product in conjunction with other techniques when using the product to stop bleeding and stresses that the device is still safe to use as labeled.
【Original Information】
FDA classifies recall of Boston Scientific device as ‘most serious’
2024-04-17 , KFGO
感谢本期日报的审核者:mildbreeze,章台柳,圆圈儿,RZN,九卿臣,Johnson,MD,Richard,lxx
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0414 | A review of the high-scoring Cell sub-journal, an article about fermented foods
0413 | 3 major articles in the sub-journal to analyze the current situation and future of microbiome therapy
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