On April 11, we interpreted 15 articles focusing on: intestinal immunity, pathogens, fungi, bacterial interactions, intestinal colonization, oral bacteria, small intestinal flora, altitude, antibiotic resistance, Akeso, Bristol-Myers Squibb, AbbVie, Tongyi Pharmaceutical, Gan & Lee Pharmaceutical.
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Nature: Colon cells talk to T cells to protect the gut from germs
Nature——[64.8]
(1) In this study, we explored the immune response mechanism of intestinal epithelial cells to infection with the intestinal pathogen Citrobacterium murine (Cr) by scRNA-seq, mouse models, and cell experiments, and (2) found that there were two subsets of absorbent colonic epithelial cells in mice, namely the DCC subset located in the middle and distal colon and the PCC subset similar to small intestinal enterocytes located in the proximal colon, which showed different characteristics (such as differential response to IL-22) during Cr infection;(3) Cr mainly targets DCC, which accelerates aging and shedding after Cr infection, while up-regulating IL-22-induced defense genes, such as S100a family antimicrobial peptides, and the chemokines CXCL2 and CXCL5, which recruit neutrophils, and these reactions work together to promote pathogen clearance;(4) Intestinal epithelial cells induce CD4 T cells to produce sustained IL-22 signaling by expressing MHCII for antigen presentation, which plays a key role in limiting Cr infection;(5) These findings explain the colonization of Cr in a specific area of the colon (the mid and distal colon) and reveal the mechanisms by which intestinal epithelial cells coordinate immune protection by talking to T cells.
【Original Information】
Distal colonocytes targeted by C. rodentium recruit T-cell help for barrier defence
2024-04-10, doi: 10.1038/s41586-024-07288-1
Discovery of new commensal fungi may alleviate candidiasis
Journal of Experimental Medicine——[15.3]
(1) In this study, a novel intestinal symbiotic fungus, Kazachstania heterogenica var. weizmannii (Kw), was discovered, which attenuated candidiasis by competing for symbiosis with Candida albicans;(2) The isolation of a novel commensal fungus, Kw, in the intestinal tract of mice, inhibited intestinal colonization of Candida albicans and significantly reduced the load of Candida albicans in vivo;(3) After immunosuppression of Candida albicans-colonized mice, the competitive symbiosis of Kw could alleviate fatal candidiasis in mice;(4) Metagenomic analysis showed that K. albicans was found to be successful. heterogenica or K. Weizmannii is also present in commensal fungi in humans;(5) This study reveals a competitive fungal symbiosis in the gut microbiota independent of bacterial and immune responses, providing a potential strategy for the treatment of diseases caused by Candida albicans.
【Original Information】
Competitive fungal commensalism mitigates candidiasis pathology
2024-03-18, doi: 10.1084/j.20231686
How does Klebsiella pneumoniae kill intestinal competitors?
ISME Journal——[11]
(1) About 80% of the highly virulent Klebsiella pneumoniae (HvKp) isolates belonged to clonogroup 23 sublineage I (CG23-I), which had obtained genomic islands GIE492 and ICEKp10;(2) In this study, 12361 Klebsiella genomes were analyzed, and the virulence islands GIE492 and ICEKp10 were co-related with CG23-I and CG10118 HvKp lineages;(3) GIE492 and ICEKp10 encoded bacteriocin microcin E492 (mccE492) and the genotoxin colibactin enhanced the colonization ability of HvKp in the intestine, and colibactin dominated the change of microbial diversity;(4) In vitro experiments showed that colibactin and mccE492 could kill or inhibit a variety of gram-negative bacteria such as Klebsiella and Escherichia coli, as well as a variety of gram-positive bacteria such as Bifidobacterium and Trichilla.(5) The results showed that mccE492 disrupted the bacterial cell membrane and made the genotoxin colibactin better enter the cell to achieve genotoxicity, and the acquisition of the two virulence islands may help HvKp better colonize the host, explaining the dominance of the CG23-I lineage.
【Original Information】
Hypervirulent Klebsiella pneumoniae employs genomic island encoded toxins against bacterial competitors in the gut
2024-03-28 , doi: 10.1093/ismejo/wrae054
Intestinal pathogens use glucuronic acid to promote intestinal colonization
PNAS——[11.1]
(1) This study revealed the role of glucuronic acid (GlcA) in intestinal colonization of intestinal pathogens such as Citrobacterium;(2) Treatment with microbial β-glucuronidase inhibitor (GUSi) in mice could reduce the colonization of Citrobacterium in the host intestine without affecting bacterial virulence, host inflammatory response and intestinal microbiota composition;(3) GlcA as a carbon source provided an advantage for citrobacter proliferation, and compared with the wild type, mutants unable to metabolize GlcA had less colonization in the gut than the wild type;(4) Symbiotic E. coli lacking β-glucuronidase can reduce the colonization of Citrobacterium in the gut;(5) This study suggests that GlcA is not used as a signal-activated pathogen virulence, but is utilized as a metabolite, providing the possibility for the development of novel therapeutic strategies for intestinal infections.
【Original Information】
Glucuronic acid confers colonization advantage to enteric pathogens
2024-03-19 , doi: 10.1073/pnas.2400226121
How do oral pathogens migrate and adapt to the gut?
Gut Microbes——[12.2]
(1) high-density transposon screening to identify genes for oral Klebsiella strains that need to adapt to oral and intestinal mucosal homeostasis and inflammation;(2) The oral pathogen Klebsiella aerogenes was associated with oral and intestinal inflammation in mice, and a genomic locus called the inflammatory intestinal colonization site (LIG) encoding genes associated with iron uptake and host adhesion was identified;(3) The LIG locus was highly conserved in Klebsiella aerogenes strains, and these genes were also present in several other Klebsiella species;(4) Transposon screening showed that the LIG locus was essential for the adaptation of Klebsiella aeolia to non-native sites, especially the colonization of the CUP1 system in the inflammatory gut rather than in the oral mucosa;(5) This study suggests that oral pathogens may utilize a different adaptation mechanism than the native site when ectopic colonization of the intestine.
【Original Information】
Oral pathobiont Klebsiella chaperon usher pili provide site-specific adaptation for the inflamed gut mucosa
2024-03-28 , Yogurt: 10.1080/19490976.2024.2333463
Transcriptome mapping of Bacteroides multiforme reveals small RNAs that regulate tetracycline sensitivity
Nature Microbiology——[28.3]
(1) Transcriptional unit localization of the intestinal bacterium Bacteroides multiforme using differential RNA sequencing (RNA-seq) and conventional RNA sequencing to analyze the expression levels of Bacteroides multiforme under 15 in vivo growth conditions, and to infer the transcriptional regulatory network of specific stress and carbon sources, (2) to expand the annotation of small RNAs (sRNAs) and combine with published transposon mutant suitability data to predict sRNA important under specific conditions, and (3) to detect a sRNA named sRNA MasB was able to downregulate tetracycline tolerance, identify potential targets of MasB through MS2 affinity purification and RNA sequencing techniques, and evaluate its role in MasB-related phenotypes;
【Original Information】
An expanded transcriptome atlas for Bacteroides thetaiotaomicron reveals a small RNA that modulates tetracycline sensitivity
2024-03-25, doi: 10.1038/s41564-024-01642-9
Nature: Interaction between microbial communities of breeders and cattle
Nature Microbiology——[28.3]
(1) a one-year longitudinal analysis of the nasal and fecal microbiomes of 66 dairy farmers and 166 dairy cows to explore the dynamic association of microbiome and antimicrobial resistance genomes between farmworkers and livestock; (2) the microbial communities of dairy farmers were also compared to 60 people (non-farmers) without occupational exposure to agricultural animals matched by age, sex and zip code; The nasal bacterial communities of dairy farmers were more diverse than those of non-farm workers, and there were more shared microbial lineages in the gut microbial community between dairy farmers and cows on the same farm, and (4) these shared microbes were associated with antibiotic resistance genes, demonstrating the interconnectedness of human and animal microbial communities.
【Original Information】
Longitudinal dynamics of farmer and livestock nasal and faecal microbiomes and resistomes
2024-04-03, doi: 10.1038/s41564-024-01639-4
Domestic team: changes in intestinal microbiota and serum metabolome at high altitudes
Microbiome——[15.5]
(1) The team of He Kunlun and Xiaojing Zhao from 301 Hospital published a study revealing the effects of high altitude environment on the intestinal microbiota and plasma metabolome of healthy young men, as well as its dynamic relationship with altitude change;(2) The study found that the intestinal microbiota of Han individuals gradually converged with that of Tibetan people as they migrated from low altitude to high altitude, but they returned to low altitude again;(3) A total of 51 species were identified in the process of adaptation to high altitude, and 57 species were identified in the process of deadaptation;(4) (5) Similar to Tibetan, a total of 41 metabolites were elevated in Han individuals after climbing to high altitude, and the significant changes in host plasma metabolome and clinical indicators were mainly explained by changes in intestinal microbiota composition, (6) Sterile animal experiments showed that some species exhibiting altitude-dependent changes in the population may play a key role in host purine metabolism.
【Original Information】
Longitudinal multi-omics analysis uncovers the altered landscape of gut microbiota and plasma metabolome in response to high altitude
2024-04-05, doi: 10.1186/s40168-024-01781-5
Small intestinal microbiota: from composition to metabolism (review)
Trends in Microbiology——[15.9]
(1) Through advanced sampling and multi-omics techniques, the taxonomic composition and functional potential of the small intestinal microbiota (SIM) were deeply explored, providing a new perspective for improving intestinal health;(2) SIM is composed of five core genera, which are abundant and high in the whole small intestine, accompanied by specific intestinal segments;(3) SIM plays a crucial role in carbohydrate degradation, amino acid metabolism, lipid absorption, and micronutrient metabolism;(4) Small intestinal bacterial overgrowth can be divided into two categories: small intestinal oral bacterial overgrowth (SIOBO), which is characterized by oral gram-positive bacterial overgrowth, and small intestinal bacterial overgrowth (SIBO), which is characterized by overgrowth of Enterobacteriaceae bacteria, such as Escherichia coli or Klebsiella;(5) SIOBO may cause environmental bowel disease and growth retardation.
【Original Information】
Small intestinal microbiota: from taxonomic composition to metabolism
2024-03-18, Doi: 10.1016/J.Tim.2024.02.013.
The relationship between enteric microbiota and obesity
American Journal of Gastroenterology——[9.8]
(1) This study revealed the microbiome characteristics and their association with metabolic and inflammatory biomarkers in normalweight, overweight, and obese populations by analyzing duodenal microbiome and serum biomarkers;(2) Duodenal microbial signatures in overweight individuals included decreased relative abundance of Bifidobacterium and Escherichia coli K-12 strains, and increased relative abundance of Lactobacillus enterobacteria, Lactobacillus johnesi and Prevotella loeschii;(3) Obesity-specific microbial signatures include an increase in the relative abundance of Lactobacillus gasselli and a decrease in the relative abundance of Lactobacillus reuteri (murine subsp. murine subsp., Alloprevotella rava), and Ciliate species, (4) with the change of body weight from normal to obese, the relative abundance of certain microbial species increases or decreases, and the potential of microorganisms to metabolize biogenic amines decreases, and (5) specific microbial species are associated with different types of dyslipidemia, which may provide new targets for future research and treatment.
【Original Information】
Characterization of the Small Bowel Microbiome Reveals Different Profiles in Human Subjects who are Overweight or have Obesity
2024-04-08 , Yogurt: 10.14309/Azag.0000000000002790
Akeso Biopharma announced positive results in the Phase 3 clinical trial of cadonilib in the treatment of advanced gastric cancer
(1) Recently, Akeso Biopharma announced the interim analysis results of the Phase 3 clinical study of the bispecific antibody cadonilimab injection in combination with chemotherapy for the first-line treatment of advanced gastric cancer;(2) The study showed that the combination of cadonilimab compared with chemotherapy can significantly prolong the overall survival and reduce the risk of death, and showed excellent efficacy even in the population with low PD-L1 expression;(3) In January 2024, the New Drug Authorization Application submitted by Akeso Biopharma in combination with chemotherapy for the first-line treatment of advanced gastric cancer has been accepted by the National Medical Products Administration;(4) At present, Akeso has developed more than 50 innovative drug candidates, 19 of which have entered the clinical stage, 3 new drugs have been commercialized, and 5 new drug applications are under review.
【Original Information】
The positive results of the phase III clinical trial of the first-line treatment of advanced gastric cancer were released
2024-04-08 , 康方生物Acheese
Bristol-Myers Squibb Announces New Positive Results from Kralati for CRC
(1) Bristol-Myers Squibb presented updated data from the KRYSTAL-1 clinical trial at the 2024 American Association for Cancer Research Annual Meeting on April 9, (2) the trial evaluated the efficacy and safety of Krasati in combination with cetuximab in patients with advanced or metastatic colorectal cancer (CRC) with KRAS G12C mutations, and (3) 85% of patients had controlled disease, an objective response rate of 34%, and a median progression-free survival of 6.9 months; Bristol-Myers Squibb has submitted a supplemental new drug application and the FDA has granted priority review status with a PDUFA target action date of June 21, 2024.
【Original Information】
85% of advanced cancers are under control!Positive results from Bristol-Myers Squibb's latest trial of KRAS inhibitors announced
2024-04-09 , 药明康德
艾伯维确认收购Landos Biopharma
(1) AbbVie recently confirmed that it plans to complete the acquisition of Landos Biopharma, a biopharmaceutical company, in the second quarter of 2024, (2) Landos Biopharma, a company focused on developing novel oral therapeutics for the treatment of autoimmune diseases, including Crohn's disease and ulcerative colitis, and (3) AbbVie will acquire Landos Biopharma's lead investigational drug, NX-13, a potentially first-in-class oral NOD-like receptor X1 (NLRX1) agonist, (4) NX-13 is currently in a Phase 2 clinical NEXUS study to evaluate its safety and efficacy in patients with moderate to severe ulcerative colitis, and if approved, NX-13 will further strengthen AbbVie's pipeline in the field of inflammatory bowel disease.
【Original Information】
AbbVie to Acquire Landos Biopharma and Novel Ulcerative Colitis Investigational Drug
2024-04-09 , managed healthcare executive
Tongyi Therapeutics' CBP-1019 was granted orphan drug designation by the FDA for the treatment of esophageal cancer
(1) On April 9, Tongyi Pharma announced that its self-developed CBP-1019 drug has been granted orphan drug designation by the FDA for the treatment of esophageal cancer;(2) CBP-1019 has previously received orphan drug designation from the FDA for the treatment of pancreatic cancer;(3) CBP-1019 is a second-generation product based on Bi-XDC technology, which is suitable for a variety of tumors and has significant anti-tumor activity and good safety profile;(4) the global five-year survival rate for esophageal cancer is generally less than 10% According to GLOBOCAN, about 55% of esophageal cancer patients in China are in urgent need of new drugs to improve treatment outcomes.
【Original Information】
CBP-1019 received orphan drug designation from the FDA again
2024-04-09 , Tongyi Pharmaceutical
Gan & Lee Pharmaceutical's oral GZR18 tablets completed the administration of the first patient in the phase 1 clinical trial
(1) On April 8, Gan & Lee Pharmaceutical announced that its self-developed oral peptide GLP-1 receptor agonist GZR18 tablets have completed the dosing of the first subject in the phase 1 clinical study in China;(2) GZR18 tablets are designed to treat type 2 diabetes mellitus, and this clinical trial plans to enroll 116 healthy adult subjects;(3) the trial is designed to evaluate the bioavailability, pharmacokinetics, pharmacodynamics, safety and tolerability of GZR18 tablets in adult healthy subjects in China;(4) (5) GZR18 injection has been studied in China and the United States, and its safety and efficacy have been confirmed, and it has entered the phase 2 clinical research stage.
【Original Information】
Gan & Lee Pharmaceutical's oral GZR18 tablets completed the administration of the first subject in the phase I clinical trial
2024-04-08 , Gan & Lee Pharmaceutical
感谢本期日报的审核者:mildbreeze,圆圈儿,Johnson,九卿臣,Bingbing,Richard
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