On April 24, we interpreted 15 articles of literature, focusing on: neurodegenerative diseases, gut-brain axis, gender differences, depression, prognostic markers, 5G, gut-bone axis, microplastics, SNIPR Biome, BMS, Merck, OMNY Health, Anaerobic Biology, Changguang Chenying.
The daily newspaper was published by R. AI-assisted creation generation, manual review and proofreading.
Liu Zhihua + Huang Chaolan + Cao Li et al.: Analysis of the intestinal mechanism of hereditary neurodegenerative diseases
Protein & Cell——[21.1]
(1) Progressive myoclonic epilepsy (an inherited neurodegenerative disease) caused by SCARB2 gene defects, Liu Zhihua's team at Tsinghua University, Huang Chaolan's team from Peking Union Medical College, Chinese Academy of Medical Sciences, and Cao Li's team from the Department of Neurology of the Sixth People's Hospital of Shanghai Jiao Tong University published a study to reveal the intestinal mechanism in this disease; (2) Scarb2 gene deletion led to age-dependent dietary lipid malabsorption accompanied by vitamin E deficiency in mice;(3) Scarb2 deficiency is related to the imbalance of intestinal microbiota and changes in the bile acid pool, resulting in overactivation of intestinal FXR, which in turn impairs intestinal epithelial cell renewal and lipid absorption;(4) The vitamin E level in patients with SCARB2 gene mutation is severely reduced, and dietary vitamin E cannot be absorbed;(5) Inhibition of FXR or vitamin E supplementation can improve neuromotility and neuropathy in Scarb2 knockout mice;(6) This study suggests that SCARB2-related neurodegenerative diseases may be ameliorated by addressing nutritional deficiencies and gastrointestinal problems.
【Original Information】
Gut dysbiosis impairs intestinal renewal and lipid absorption in Scarb2 deficiency-associated neurodegeneration
2024-04-18 , doi: 10.1093/procel/pwae016
Domestic team: Toxoplasma gondii infection or through intestinal flora injury cognition
Brain Behavior and Immunity——[15.1]
(1) The team of Pan Wei and Yu Yinghua of Xuzhou Medical University and the team of Yin Kun of Shandong First Medical University found that changes in intestinal microbiota can lead to cognitive deficits caused by chronic infection of Toxoplasma gondii;(2) Toxoplasma gondii infection leads to synaptic structural damage and neuroinflammation in the hippocampus in mice, accompanied by intestinal dysbiosis, impaired barrier integrity and inflammation in mice;(3) Broad-spectrum antibiotic treatment can alleviate the adverse effects of Toxoplasma gondii infection on cognitive function in mice, while fecal bacteria transplantation can transfer cognitive deficits and hippocampal pathological changes in infected mice to healthy mice;(4) The abundance of butyric acid-producing bacteria and serum butyrate levels were significantly reduced in infected mice, and butyric acid supplementation could improve cognitive impairment caused by Toxoplasma gondii infection;(5) The decrease in butyrate levels was negatively correlated with the level of anti-Toxoplasma IgG antibodies in human subjects compared with healthy controls;(6) This study showed that gut microbiota is a key regulator of cognitive impairment caused by Toxoplasma gondii.
【Original Information】
Alterations in gut microbiota contribute to cognitive deficits induced by chronic infection of Toxoplasma gondii
2024-04-10 , doi: 10.1016/j.bbi.2024.04.008
Sex-specific association of Alzheimer's disease genotype with gut microbiota in mice
Alzheimer's and Dementia——[14]
(1) The sex-specific association between the gut microbiota of human-derived amyloid precursor knock-in (hAβ-KI) mice and the genotype of Alzheimer's disease (AD) was explored;(2) Through metagenomic and non-targeted metabolomics analysis, it was found that the intestinal microbiota of 18-month-old female hAβ-KI mice was significantly different from that of wild-type mice, and the AD genotype explained 18% of the microbiota variation;(3) The metabolome diversity of female hAβ-KI mice was different, but there was no significant difference in individual metabolites;(4) The microbial community of hAβ-KI mice can be distinguished from early-onset AD model mice, mainly driven by Romboutsia ilealis and Turicibacter spp.(5) Cage assignment contributes more than 40% to the variation of microbiota and metabolome, emphasizing the importance of considering microbiota when designing AD mouse model studies.
【Original Information】
Sex-specific associations between AD genotype and the microbiome of human amyloid beta knock-in (hAβ-KI) mice
2024-04-04, doi: 10.1002/al-dha.13794
Does antibiotic treatment reduce seizures?
Brain Behavior and Immunity——[15.1]
(1) This study found that treatment with the antibiotic rifaximin in the early stages of epilepsy can reverse intestinal changes and reduce seizure duration in mice, enhancing the effect of gut-based epilepsy treatment;(2) Rifaximin administered for 21 days in the early stage of the disease (within 24 hours after seizures) can significantly reduce the duration of seizures in mice and prevent the loss of hippocampal lichen cells;(3) Compared with the epilepsy mice on the control diet, the intestinal structural and cellular changes were reversed, the intestinal barrier integrity was enhanced, and the expression of inflammatory markers was reduced in the mice treated with rifaximin;(4) Rifaximin had no significant effect on the number and duration of seizures and did not affect the intestine when administered to mice with chronic epilepsy (51 days postictal) for 21 days;(5) Rifaximin altered the α and β diversity of gut microbiota in mice at both disease stages, and these changes correlated with disease stages, with the abundance of specific microbiota in early disease stages positively correlated with the duration of epilepsy in mice.
【Original Information】
Early treatment with rifaximin during epileptogenesis reverses gut alterations and reduces seizure duration in a mouse model of acquired epilepsy
2024-04-10 , doi: 10.1016/j.bbi.2024.04.007
Molecular magnetic resonance imaging of intestinal MAdCAM-1: prognostic biomarkers for multiple sclerosis
Brain Behavior and Immunity——[15.1]
(1) This study revealed the interaction between intestinal inflammation and multiple sclerosis (MS), and proposed molecular magnetic resonance imaging (MRI) of intestinal mucosal address cell adhesion molecule-1 (MAdCAM-1) as a new biomarker for MS prognosis, (2) disease severity was positively correlated with MAdCAM-1 MRI signal in two experimental autoimmune encephalomyelitis (EAE) models, and (3) high MAdCAM-1 in the asymptomatic phase MRI signals are associated with delayed onset of progressive EAE and reduced risk of recurrent EAE transitioning to secondary progressive, (4) the decrease in CD4+ T cells and B lymphocytes in the gut coincides with the increase in these cells in the spinal cord as the disease progresses, i.e., bidirectional immune communication between the gut and the central nervous system, and (5) this study provides new perspectives and potential targets for the early diagnosis and treatment of MS.
【Original Information】
Intestinal MAdCAM-1 imaging as biomarker for prognostic in murine models of multiple sclerosis
2024-04-09 , doi: 10.1016/j.bbi.2024.04.006
Stress reduces mucin 13 and changes intestinal bacteria to promote depression
Brain Behavior and Immunity——[15.1]
(1) To explore the role of mucin 13 (Muc13) as an upstream regulator of microbial composition changes under the background of stress, (2) the expression of intestinal glycoprotein Muc13 decreased significantly after psychological stress exposure, and the decrease of Muc13 was mediated by the Hnf4 transcription factor family; (3) Targeting the Muc13 gene was sufficient to induce changes in intestinal microbiota composition and desperate behavior, highlighting the key role of Muc13 in maintaining microbial and behavioral homeostasis; (4) In this study, we revealed the mechanism of stress-induced microbial changes and explored new regulators of Muc13 expression.
【Original Information】
Stress-induced mucin 13 reductions drive intestinal microbiome shifts and despair behaviors
2024-04-03 , doi: 10.1016/j.bbi.2024.03.028
Domestic team: 5G communication frequency radiation causes anxiety or due to intestinal dysbiosis
Science of the Total Environment——[9.8]
(1) The team of Ding Guirong of the Air Force Medical University and the team of Wang Chunping of Shandong Second Medical University revealed the effects of 3.5GHz radio frequency radiation (a common frequency used in 5G communication) on the intestinal flora, brain metabolites and behavior of mice, and found that it mediated anxiety-like behavior through NLRP3 inflammasome-dependent neuronal pyroptosis;(2) 3.5GHz radio frequency radiation for 1 hour a day for 35 consecutive days induced anxiety-like behavior in mice, accompanied by NLRP3-dependent neuronal pyroptosis in the CA3 region of the hippocampus;(3) (4) 3.5 GHz RF radiation also caused significant changes in metabolites in feces, serum and brain, which were mainly enriched in glycerophospholipid metabolism, tryptophan metabolism and arginine biosynthesis;(5) Correlation analysis showed that the dysbiosis of intestinal microbiota was related to differential metabolites;(6) This study found that intestinal dysbiosis and its metabolites may be involved in radiofrequency-induced anxiety-like behaviors through neuronal pyroptosis in the brain, providing a new perspective for understanding the neurotoxicity induced by 5G radiofrequency radiation.
【Original Information】
Intestinal microbiota via NLRP3 inflammasome dependent neuronal pyroptosis mediates anxiety-like behaviour in mice exposed to 3.5 GHz radiofrequency radiation
2024-04-10 , doi: 10.1016/j.scitotenv.2024.172391
The anti-inflammatory drug DIZE exerts an anti-inflammatory effect through the gut-brain-spleen axis
Brain Behavior and Immunity——[15.1]
(1) This study found that the anti-inflammatory drug Diminazene aceturate (DIZE) attenuated the systemic inflammatory response in male mice by modulating the gut microbiota-5-HT brain-spleen sympathetic axis;(2) In the endotoxemia model, DIZE treatment resulted in hyporesponsiveness to inflammatory signals in mice and promoted inflammatory reflex activation to reduce inflammation;(3) Unilateral cervical vagus nerve resection did not affect the anti-inflammatory effect of DIZE in spleen and serum, while splenic nerve resection reduced tumor necrosis factor (TNF) synthesis in spleen and serum;(4) LPS modulates intestinal microbiota to induce intestinal inflammation and reduce serum levels of tryptophan and serotonin (5-HT), whereas DIZE restores serum tryptophan levels and increases hypothalamic 5-HT levels;(5) 5- HT synthesis inhibitor 4-chloro-DL-phenylalanine (pcpa) can eliminate the anti-inflammatory effect of DIZE in the spleen;(6) This study revealed that DIZE increases the level of central 5-HT through intestinal microbiota regulation and activates the sympathetic branch of the inflammatory reflex to control TNF production in the spleen of endotoxemic mice.
【Original Information】
Diminazene aceturate attenuates systemic inflammation via microbiota gut-5-HT brain-spleen sympathetic axis in male mice
2024-03-26 , doi: 10.1016/j.bbi.2024.03.037
Army Medical University: Melatonin, a metabolite of the intestinal flora, may be used to treat osteoporosis
Journal of Pineal Research——[10.3]
(1) The team of Luo Fei, Xu Jianzhong, Sun Dong and Yueqi Chen from the Army Medical University found that the tryptophan metabolite melatonin (MLT) produced by intestinal microbes helps improve osteoporosis (OP) by regulating the metabolism of short-chain fatty acids (SCFA) and trimethylamine oxide (TMAO) ;(2) OP leads to intestinal tryptophan disorder and decreased microbiota production of MLT, and MLT supplementation can alleviate OP-related clinical symptoms and reverse intestinal microbiota dysbiosis, including improving intestinal flora diversity, Increase the relative abundance of probiotics (such as Allobaculum and Parasutterella) and improve the metabolic function of intestinal microbiota, such as amino acid metabolism, nucleotide metabolism and energy metabolism;(3) MLT significantly increases the production of short-chain fatty acids and reduces the metabolites associated with TMAO;(4) MLT can regulate the homeostasis of M1/M2 macrophages, reduce the level of pro-inflammatory cytokines in serum, and restore intestinal barrier function;(5) These findings provide new insights into MLT as a potential drug for the treatment of OP.
【Original Information】
Gut microbially produced tryptophan metabolite melatonin ameliorates osteoporosis via modulating SCFA and TMAO metabolism
2024-04-15 , Yogurt: 10.1111/JPI.12954
Ingested microplastics can enter different tissues throughout the body and affect metabolism
Environmental Health Perspectives——[10.4]
(1) Exposure to microplastics was simulated by oral ingestion of a mouse model to study their accumulation in different tissues in the host and their effects on tissue metabolic activity;(2) Mice were dosed with polystyrene (PS) microspheres and PS, polyethylene (PE) and polylactic acid-glycolic acid copolymer (PLGA) microspheres twice a week for four weeks, and then different tissues were collected for microsphere microscopic examination and metabolomics detection; (3) The results showed that microplastic particles could penetrate the intestinal barrier and exhibit microplastic particles in mouse serum, brain, (4) Microplastic exposure led to metabolic profile changes in colon, liver and brain tissues, with the largest changes in colon and the smallest changes in brain, in which the dysregulated metabolic pathways were related to amino acid metabolism, and (5) there were also differences in the metabolic profiles of different host tissues between PS exposed group and mixed exposure group, among which the levels of metabolites related to nicotinate and nicotinamide metabolic pathways in the colon were the most significant.
【Original Information】
In Vivo Tissue Distribution of Polystyrene or Mixed Polymer Microspheres and Metabolomic Analysis after Oral Exposure in Mice
2024-04-10 , Yogurt: 10.1289/Ehp13435
SNIPR Biome, a bacteriophage therapy company, received $5.48 million in funding from CARB-X
(1) On April 22, SNIPR Biome announced that it had received a grant of US$5.48 million (about RMB 39.71 million) from CARB-X to advance the clinical development of pipeline drug SNIPR001; (2) SNIPR001 is a bacteriophage drug using CRISPR gene editing technology designed to prevent E. coli bloodstream infection in patients undergoing hematopoietic stem cell transplantation; (3) 1b/ The Phase 2a clinical trial, which is expected to begin later this year, will be conducted simultaneously at more than 10 clinical sites in Europe and the U.S. to investigate the safety, tolerability, pharmacokinetics, and pharmacodynamic properties of oral SNIPR001; (4) in preclinical studies, SNIPR001 be able to target clearance of antibiotic-resistant E. coli strains and excrete them in feces.
【Original Information】
SNIPR Biome receives funding from CARB-X to support advancement of CRISPRmedicine SNIPR001 into clinical trials in haematological cancer patients
2024-04-22 , SNIPR Biome
BMS ipilimumab + nivolumab for the treatment of CRC is proposed for priority review
(1) On April 22, according to the official website of the Center for Drug Evaluation of the State Food and Drug Administration, Bristol-Myers Squibb's ipilimumab injection + nivolumab injection combination therapy is proposed to be included in the priority review;(2) The proposed indications are: first-line treatment of patients with unresectable or metastatic microsatellite instability (MSI-H) or mismatch repair deficient (dMMR) colorectal cancer (CRC);(3) The combination therapy was granted Breakthrough Therapy Designation in March 2024;(4) Previous studies have shown that the combination reduces the risk of disease progression or death by 79% compared to chemotherapy, with a safety profile consistent with previous data and no new safety signals.
【Original Information】
Just now, the BMS ipilimumab + nivolumab is proposed to be included in the priority review
2024-04-23 , Pharma CMC
Merck K-drug in combination with chemotherapy for the first-line treatment of G/GEJ was approved by Health Canada for the treatment of G/GEJ
(1) On April 19, Merck announced that KEYTRUDA (pembrolizumab) in combination with chemotherapy was approved by Health Canada for the first-line treatment of adult patients with locally advanced unresectable or metastatic, HER2-negative gastric or gastroesophageal junction (G/GEJ) adenocarcinoma;(2) The approval was based on the results of the Phase 3 KEYNOTE-859 study, which showed that pembrolizumab was significantly better than placebo in overall survival (OS), (3) In terms of primary endpoint, patients who received pembrolizumab plus chemotherapy had a median OS of 12.9 months, a 22% lower risk of death compared to 11.5 months in patients receiving chemotherapy alone ;(4) In terms of secondary endpoints, patients in the Keytruda arm had a median PFS of 6.9 months and a median DOR of 8.0 months, respectively, with a 24% reduction in the risk of disease progression or death and an ORR of 51.3% , which was also higher than that of the placebo group.
【Original Information】
Health Canada Approves KEYTRUDA® as a first-line treatment for adult patients with locally advanced unresectable or metastatic HER2-negative gastric or gastroesophageal junction (GEJ) adenocarcinoma in combination with fluoropyrimidine- and platinum-containing chemotherapy
2024-04-19 , Merck
OMNY Health Launches Real-World Data Solution for Gastroenterology Research
(1) On April 22, OMNY Health announced a new real-world solution for gastroenterology research in collaboration with the nation's leading gastroenterology specialist and integrated service providers, (2) the collaboration includes more than 5,000 gastroenterology services providers serving more than 10 million patients, including United Digestive, Borland Groover and OneGI, and (3) OMNY Health is committed to improving real-world patient care and helping to address health care issues by providing greater breadth and depth of information, and (4) the partnership will support research and development in the field of gastroenterology with dedicated services including drug ordering, diagnostic testing, complication prediction, and patient clinical scoring.
【Original Information】
OMNY Health launches new GI real-world data solutions in partnership with leading US gastroenterology practices
2024-04-22 , PR Newswire
Sichuan Anaerobic Biology and Changguang Chenying have carried out strategic cooperation
(1) On April 22, Sichuan Anaerobic Biotech and Changguang Chenying signed a strategic cooperation agreement;(2) The two parties will strengthen cooperation in the field of microecological drug research and development, jointly build a human anaerobic live bacteria library, promote the construction of microbial screening and separation platform, and enhance the development of the microecological drug industry;(3) Changguang Chenying focuses on the research and development of optical and biomedical instruments, providing one-stop solutions for life science research;(4) Sichuan Anaerobic Bio is committed to the innovation of microecological live bacteria drugs, and has built a resource bank of more than 2,000 human microbial strains.
【Original Information】
Sichuan Anaerobic Biotechnology and Changguang Chenying have reached a strategic cooperation to jointly promote the development of microbial innovative drug industry!
2024-04-22 , Anaerobic Biology
感谢本期日报的审核者：圆圈儿，九卿臣，RZN，章台柳，Johnson，Richard
Click here to read the daily reports for the past 10 days:
0423 | Today's Cell: Jiang Changtao/Qiao Jie/Pang Yanli/Zheng Minghua/Jia Yanxing, etc. have made a major breakthrough in bile acids
0422 | Expert voices: Two articles in Cell focus on microbiota and cancer treatment
0421 | Food as Medicine: 10 articles focusing on dietary interventions in disease
0420 | Science揭秘：肠道中的噬菌体-病菌"军备竞赛"
0419 | Cheng Gong/Zhu Yibin/Wang Jinglin et al. Science breakthrough: clever use of symbiotic bacteria to block the transmission of mosquito-borne viruses
0418 | 聚焦特殊人群：母婴肠道菌群与健康
0417 | High-score Nature sub-journal: Bringing together the power of global players to help intestinal microbiome research
0416 | Multi-article focus: To protect the gut, no one can do without immune cells and microflora
0415 | Cell Blockbuster Review: Systematic Analysis of Cancer Complexity, the Role of Microbiota Should Not Be Underestimated
0414 | A review of the high-scoring Cell sub-journal, an article about fermented foods