In the January 27th issue of The Zealotific Daily, we deciphered 9 articles focusing on: COVID-19, sequelae, diet-microbiota interaction, engineered bacteria, bacterial cell wall peptides, Clostridium difficile, bacterial enzymes, intestinal crypts, colorectal cancer.
Huang Xiujuan's team: the relationship between intestinal flora and long-term sequelae of the new crown
Good——[23,059]
(1) 106 PATIENTS were enrolled in the hospital for 6 months from admission, and the intestinal flora and long-term sequelae of the new crown (PACS) at multiple time points were analyzed ;(2) At 6 months, 76% of the patients had PACS, and the common symptoms were fatigue, poor memory and hair loss; (3) the composition of the intestinal flora at the time of admission was related to PACS; (4) at 6 months, the composition of the microbiota of those without PACS recovered well, while the intestinal flora of PACS patients had higher levels of lively rumencoccus and Bacteroides common and lower levels of Bacterbacterium prurice; (5) Identification of intestinal flora characteristics associated with different sequelae symptoms (e.g., respiratory symptoms and neuropsychiatric symptoms and fatigue) and (6) at 6 months, butyric acid-producing bacteria had the greatest negative correlation with PACS.
【Editor-in-Chief's Comments】
Long-term sequelae of COVID-19 are common, and the reasons behind them are unclear. The team of Huang Xiujuan of the University of Chinese in Hong Kong published a new study in Gut, which studied the relationship between intestinal microbiota composition and post-acute POST-COVID-19 syndrome (PACS, which is still at least one persistent symptom 4 weeks after the new crown virus turns negative), suggesting that the composition of the intestinal flora in patients may affect susceptibility to PACS or predict the risk of sequelae of covid-19. Whether modulating the gut microbiota can help improve the sequelae of patients deserves further exploration. (@User 970937765)
【Original information】
Gut microbiota dynamics in a prospective cohort of patients with post-acute COVID-19 syndrome
2022-01-26, doi: 10.1136/gutjnl-2021-325989
Fudan University: Intestinal dysbacteriosis and intestinal barrier dysfunction, associated with the immune status of COVID-19 patients
BMC Medicine——[8.775]
(1) 63 patients with new coronary pneumonia and 8 healthy controls were included, and it was found that the intestinal flora composition of the patients changed, the comorbid species decreased, and the conditional pathogenic bacteria increased; (2) severe COVID-19 was associated with the higher abundance of 4 species, 6 microbial pathways and 10 virulence genes, and these microbial characteristics were further correlated with the host immune response; (3) human-derived proteins were identified from blood and stool samples, indicating that there was intestinal barrier dysfunction in PATIENTS WITH COVID-19; (4) increased levels of lipid polysaccharide-binding proteins in the blood of patients with severe COVID-19 , associated with blood inflammatory markers and immune cells, and disease-associated bacterial proteins can be detected in the patient's blood.
BMC Medicine published a study by Zheng Yan and Yan-Mei Chen of Fudan University as co-corresponding authors, through a multi-omics approach, the intestinal flora, intestinal barrier function and immune response of patients with new crown were analyzed, indicating that intestinal dysbacteriosis and intestinal barrier dysfunction may play a role in the pathophysiology of COVID-19 by influencing the host immune balance. (@User 970937765)
Gut microbiome alterations and gut barrier dysfunction are associated with host immune homeostasis in COVID-19 patients
2022-01-20, doi: 10.1186/s12916-021-02212-0
Tianjin University: New engineered bacteria achieve timed and fixed-point release of drugs
ACS Nano——[15.881]
(1) The dormant chamber of the dormant body not only ensures the high survival rate of microorganisms under extreme conditions (such as gastric juice), but also inhibits microbial metabolism and reduces the premature lysis of microorganisms or drugs and damage to the upper gastrointestinal tract; (3) pH-sensitive coating disintegrates in the digestive tract, and the intestine regularly awakens microorganisms to reduce the adsorption and colonization of microorganisms on the mucosa; (4) the utilization of the bionic dormant body in the intestine is higher and longer than that of unmodified microorganisms; (5) the dormant body that regularly produces neurotransmitters Lp@L30D-55 has a significant therapeutic effect on mice with Parkinson's disease, while improving the intestinal flora and increasing the abundance of probiotics.
Zheng Bin's team at Tianjin University published an article in ACS Nano, reporting a timed bionic dormant body with a established programming fate, using a sleep chamber to prevent microorganisms from being damaged by complex biological environments in vivo, while its pH-sensitive coating disintegrates in the digestive tract, which can be used to predict the metabolic time and location of microorganisms in vivo, thereby improving the utilization rate of bionic dormants and their coding drugs. This bionic dormant body may provide effective technologies for advanced microbial therapies for the treatment of various diseases. (@User 975424952)
Bionic Dormant Body of Timed Wake-Up for Bacteriotherapy
2022-01-13, doi: 10.1021/acsnano.1c08377
Cell Sub-Journal: How does diet affect the evolution of enterobacteria?
Cell Host and Microbe——[21.023]
(1) To study the evolution of Bacteroides polymorphic (Bt) in different diets (standard feed, Western-style diet, alternating between the two) after intestinal colonization in mice; (2) Bt rapidly evolved to adapt to different diets, and western-style diets chose gene mutations that promote the degradation of mucin O-glycan; (3) periodic diet alternation caused fluctuations in the frequency of such mutations, which were related to changes in the intestinal metabolic environment (especially the differences in SCFA and simple sugar content in different diets), and improved the intraspecific genetic diversity of Bt compared with constant diets ;(4) Dietary changes leave genetic markers/traits in Bt, and the genetic diversity of Bt can be used as a biomarker for individual dietary differences.
Diet can affect the composition and function of the microbiota, but the effects of diet on the evolution of gut bacteria have yet to be revealed. A new study published by Cell Host and Microbe, which looked at Bacteroides polyforme, a fiber-degrading bacterium commonly found in the gut microbiota, found that diet shaped the evolution of this bacterium in the intestines of mice, and that the genetic traits left in the bacteria (specific genetic mutations, genetic diversity) reflected the host's past diet. Changes in diet increase intraspecific genetic diversity of Bacteroides polyformis, while mutations in bacterial genes of Western-style dietary selection promote their depletion of the host's intestinal mucus layer. (@User 970937765)
Diet leaves a genetic signature in a keystone member of the gut microbiota
2022-01-26, doi: 10.1016/j.chom.2022.01.002
Nature Sub-Journal: Ornithine Metabolism and Non-Inflammatory Clostridium difficile colonization
Nature Metabolism——[13.511]
(1) Multi-omics was used to study the host colonization and molecular mechanism of action of Clostridium difficile (Cd) without pathogens by using humanized mouse models; (2) Macro transcriptome analysis of the microbiota showed that the arginine and ornithine metabolic pathways of anti-inflammatory and anti-Cd mice were upregulated in a full range compared with infected individuals; (3) Wild-type and isotoxic toxin deficiency mutant Cd infection was used to infect Sidium mice, and differential expression of L-ornithine oxidative degradation sites in Cd metabolism in non-inflammatory environments was found; (4) Individual operons encoding ornithine degradation are consistently upregulated in non-inflammatory Cd strains, both dietary and host-derived ornithine provide competitive advantages and are associated with iNOS.
Clostridium difficile (Cd) infection causes more than 200,000 hospitalizations and 13,000 deaths in the United States each year. Cd can colonize the intestines of asymptomatic carriers, causing self-infection or infection of others. Nature Metabolism published a letter that elaborates on the molecular mechanisms involved. (@User 975688480)
Oxidative ornithine metabolism supports non-inflammatory C. difficile colonization
2022-01-06, doi: 10.1038/s42255-021-00506-4
Cell Sub-Journal: Bacterial cell wall peptides promote mitochondrial homeostasis in intestinal cells
Developmental Cell——[12.27]
(1) Bacterial peptidoglycan fragments of cell wall peptides regulate Caenorhabditis elegans (C. elegans). elegans) mitochondrial homeostasis, developmental and feeding behaviors; (2) Bacterial peptidoglycan cell wall peptide enters C through disaccharide cell wall peptide effect molecules containing short AA chains. (3) Bacterial peptidoglycan cell wall peptide binds to ATP synthase as an agonist to promote its activity; (4) ATP synthase upregulates to inhibit mitochondrial oxidative stress, thereby promoting C. Elegans steady-state; (5) Given the highly conserved nature of ATP synthase, this finding has significant implications for the understanding of the interaction between animal physiology and bacterial cell metabolism.
The developmental cell published an article reporting on the role of peptidoglycan cell wall peptide derived from bacterial cells in promoting the development and foraging behavior of Caenorhabditis elegans. It is also pointed out that disaccharide cell wall peptides are effector molecules, and host ATP synthases are targets. (@User 975688480)
Bacterial peptidoglycan muropeptides benefit mitochondrial homeostasis and animal physiology by acting as ATP synthase agonists
2022-01-18, doi: 10.1016/j.devcel.2021.12.016
Jiang Weihong's team Nature sub-journal: the discovery and physiological function of new flavonoid reductase
Nature Communications——[14.919]
(1) A flavonoid reductase (FLR) specifically catalyzed flavonoids/flavonol C2=C3 bond hydrogenation reaction was found from the gut bacterium Flavonifractor plautii ATCC49531 ;(2) FLR and its crystal structure with a variety of substrates revealed the molecular basis of FLR's unique catalytic properties and identified key sites affecting enzyme activity; (3) the wide distribution of FLR and homologous proteins represents a new class of ALZ reductase that does not rely on NAD(P)H; (4) Clostridium C. ljungdahlii without FLR is unable to make effective use of flavonoids of food and drug sources; (5) FLR confers growth advantages on host bacteria in the face of flavonoid stress; and (6) flr gene is widely present in human gut bacteria.
Flavonoids are the main natural polyphenols synthesized by plants, which are not only widely present in the daily diet of humans, but also a source of many clinical drugs, with antioxidant, anti-cardiovascular disease and anti-tumor effects. The human intestinal flora can metabolize flavonoids to form active substances with different functions, and can also be transformed to affect their bioavailability, so the analytical metabolic pathway is the basis for understanding these processes. However, the metabolic mechanisms of flavonoids in the gut microbiome are currently unclear. Among them, the key enzymes responsible for initiating reactions in the metabolic pathways of flavonoids and flavonols, the main two types of compounds, have not yet been discovered and identified. A study by Weihong Jiang's research group from the Center for Excellence in Molecular plant sciences of the Chinese Academy of Sciences, published in Nature Communications, found a novel olefin reductase derived from the gut microbiome, flavonoid reductase, and revealed its key role in the metabolism of flavonoids and flavonols, two types of drug/food-derived compounds, as well as its effects on the microbiome of the gut microbiota. (@User 941615924)
Discovery of an ene-reductase for initiating flavone and flavonol catabolism in gut bacteria
2021-02-04, doi: 10.1038/s41467-021-20974-2
Nature Sub-Journal: Mechanisms of Morphological Development of the Small Intestinal Crypt
Nature Cell Biology——[28.824]
(1) Through in vivo imaging and physical model analysis during the morphological development of the crypt in the organoids of the small intestine, it is found that the formation of the crypt is accompanied by a sharp decrease in the space in the cavity of the organoid; (2) the high expression of myosin in the basement membrane of chorionic tissue and the apical membrane of the crypt causes the spontaneous curvature of the tissues of the small intestine organoids to promote the formation of the crypt; (3) the reduction of the space in the cavity of the small intestine is a necessary condition for the formation of the crypt; (4) once the crypt is formed, even if the volume of the cavity is increased, the structure of the crypt that has been formed will not be eliminated; (5) The highly expressed sodium-glucose synergistic transporter SGLT1 by small intestinal epithelial cells reduces the volume of the cavity by regulating the osmolal pressure of cells and absorbing fluid in the cavity.
As an in vitro culture system, organoids are more likely to perform large-scale imaging-based phenotypic analyses at the single-cell and molecular levels than mammalian models. The development of the small intestinal crypt in organoids begins with the appearance of Paneth Cell. Pan's cells secrete stem cell inducers such as Wnt to promote stem cell production. Stem cells and Pan's cells aggregate to form crypt tissue, which bulges and gradually develops into mature bud-like structures. This structure is essential for the crypt to maintain the small intestine stem cell pool, but due to the difficulty of inoperative study of the small intestine, the developmental process and mechanism of this morphogenesis have long been insufficiently studied. A study published in Nature Cell Biology used small intestinal organoids to conduct a groundbreaking study of the morphological development mechanism of the intestinal crypt, revealing that in the process of mammalian organ development, not only is the mechanical force on the cell membrane produced by non-myoscellular myosin regulating the morphogenesis of tissues, but also that liquid-related forces such as osmotic pressure are involved in driving the process, and that different kinds of forces are coordinated with each other and interlocked with cell differentiation and physiological functions of different cell types. In the end, multiple guarantees that the organizational form is formed in a timely and appropriate manner, reflecting the exquisite design of the evolution of organisms in development. (@User 941615924)
Cell fate coordinates mechano-osmotic forces in intestinal crypt formation
2021-06-21, doi: 10.1038/s41556-021-00700-2
White cheese and sugary dairy products may increase the risk of colorectal cancer
International Journal of Cancer——[7.396]
(1) Of the 101,279 participants enrolled, a median follow-up of 5.9 years resulted in a total of 2503 cancers (including 783 breast cancers, 323 prostate cancers and 182 colorectal cancers) ;(2) total dairy intake was not significantly associated with overall cancer risk; (3) fromage blanc was significantly associated with an increase in overall cancer risk (HR=1.11) and colorectal cancer risk (HR=1.39); Sugary dairy intake was significantly associated with increased risk of colorectal cancer (HR=1.58) ;(5) Dairy intake was not significantly associated with prostate and breast cancer risk.
The results of a prospective cohort study published in the International Journal of Cancer, which followed more than 100,000 subjects for many years, found that total dairy intake was not significantly associated with overall cancer risk, but that intake of white cheese and sugary dairy products was associated with an increased risk of colorectal cancer, while white cheese intake was also associated with an increased overall cancer risk. （@aluba）
Dairy product consumption and risk of cancer: a short report from the NutriNet-Santé prospective cohort study
2022-01-18, doi: 10.1002/ijc.33935
Thanks to the creators of this issue of the daily: user 970937765, chenfen, user 947409196, user 975688480, user 979095724, user 941615924, aluba
Click to read the daily newspaper for the past 10 days:
01-26 | The Lancet's 27-page essay focuses on the systematic analysis of the dangers of antibiotics and drug resistance
01-25 | 7 Articles focus on enteritis: common toothpaste components / too much glucose damage bacteria to the intestines?
01-24 | Wuda Zhang Xianzheng waited for a breakthrough in the brain hole: using engineered yeast to "drunk" cancer cells
01-23 | Non-stop feeding, non-stop nutrition: 9 articles at a glance at the latest dietary research progress
01-22 | Microbiota-gut-brain axis: 9 articles at a glance at recent research advances
01-21 | finally! NEJM publishes phase 3 positive results for the first flora drug
01-20 | Guo Chunjun et al. Cell breakthrough: successfully edited dozens of non-mode intestinal bacteria genes
01-19 | 60.6 points of review: How bacteriocins shape the microbiota
01-18 | Honey of Ru, Arsenic Cream of Peter: "Good" fat or aggravated enteritis?
01-17 | "Nature Review" published 2 articles in detail: mechanical sensation in the gastrointestinal tract