Within-host evolution of a gut pathobiont facilitates liver translocation.

2024/06/2300:28:33 science 1867

Within-host evolution of a gut pathobiont facilitates liver translocation. - DayDayNews

Within-host evolution of a gut pathobiont facilitates liver translocation. - DayDayNews

0 In the July 14 issue of "Warm Heart Daily", we interpreted 9 documents, focusing on: bacterial evolution, ILC3, intestinal stem cells, intestinal virome, gut-brain axis, nanomedicine, Bifidobacterium , Bacteroides thetaiotaomicron, parasitic. ​​


Nature: Enterobacteriaceae can evolve pathogenic translocation capabilities within the host

Nature——[69.504]

① Combining in vivo evolution experiments and comparative genomics analysis, it was found that the intestinal pathogenic symbiotic bacterium Enterococcus gallinarum (Eg) can Multiple lineages have evolved to adapt to the different intestinal microenvironments of mice (intestinal lumen vs mucosa); ② Different Eg strains have different characteristics: compared with strains adapted to the intestinal lumen, strains adapted to the intestinal mucosa can escape the host The immune detects and clears it, translocates across the intestinal barrier and survives in the mesenteric lymph nodes and liver, and causes intestinal and liver inflammation; ③ This is related to strain-specific regulatory gene mutations, gene expression program changes and cellular changes. It is related to the remodeling of wall structure; ④ In other intestinal bacteria (such as Lactobacillus rhamnosus ), there is also a phenomenon of divergent evolution to adapt to the intestinal lumen or mucosa, but the translocation ability is related to the bacterial species.

[Editor’s comment]

Over time, the symbiotic microorganisms colonizing our intestines continue to adapt and evolve. Yale University Noah Palm's team proposed a hypothesis in the latest study published in Nature, believing that the evolution of commensal enterobacteria in the host may affect their pathogenic tendencies. They tested this hypothesis using a pathogenic commensal bacterium, Enterococcus gallinarum, as a model. This bacterium can translocate to tissues and organs such as the liver in susceptible mice, thereby causing autoimmune diseases. By analyzing the isolate in mouse feces and liver, we found that this bacteria can spontaneously undergo divergent evolution within the host, producing different lineages adapted to the intestinal lumen or intestinal mucosa. Among them, strains adapted to the intestinal mucosa have invasive and pathogenic characteristics, including translocation to the liver, immune evasion, and inflammation; in contrast, strains adapted to the intestinal lumen are more "good" (and may be more transmissible) ). In short, this study provides a new perspective for understanding the occurrence and development of microbial-related diseases at the strain level and time scale, which can, to a certain extent, explain the "stochasticity" and age-relatedness that exist in microbiota-driven diseases. (@mildbreeze)

【Original information】

Within-host evolution of a gut pathobiont facilitates liver translocation

2022-07-13, doi: 10.1038/s41586-022-04949-x


Nature: A new ILC3 subpopulation that protects intestinal homeostasis

Nature ——[69.504]

① Single-cell RNA sequencing of mouse intestinal RORγt+ immune cells found that the transcription factor ZBTB46 is expressed in the CCR6+ type 3 innate lymphocyte (ILC3s) subpopulation; ② ZBTB46 was previously considered a conventional dendritic cell (cDC) specific marker, the development and phenotype of ZBTB46+ ILC3s are different from cDC; ③ The expression of ZBTB46 in ILC3s requires RORγt, is regulated by the bacterial flora (downregulated after bacterial colonization), and is upregulated by inflammatory cytokines ; ④ ZBTB46 limits the pro-inflammatory properties of ILC3s: inhibiting OX40L-dependent Th17 expansion and intestinal inflammation after infection; ⑤ ZBTB46+ ILC3s are an important source of IL-22, and the lack of this cell subset will increase the intestinal pathogenicity of mice. Susceptibility to bacterial infections and associated intestinal inflammation.

[Editor's comment]

RORγt is a transcription factor specialized in the lineage of immune cells. It is expressed in helper T cells 17 (Th17), regulatory T cells (Treg), γδ T cells and type 3 innate lymphocytes (ILC3s). ) and other intestinal immune cells, these immune cells play a key role in maintaining intestinal homeostasis and resisting infection. However, there are still many unknowns about the cellular heterogeneity, regulatory mechanisms of RORγt+ immune cells, and the functional characteristics of different subpopulations . Nature recently published research from Gregory Sonnenberg's team at Cornell University in the United States, identifying a new LTi-like ILC3s subpopulation, which is characterized by the expression of the conventional dendritic cell marker ZBTB46. This study further revealed the expression regulation and function of ZBTB46 in ILC3s, as well as the characteristics of ZBTB46+ ILC3s and their important role in intestinal homeostasis.(@mildbreeze)

[Original information]

ZBTB46 defines and regulates ILC3s that protect the intestine

2022-07-13, doi: 10.1038/s41586-022-04934-4


Nature: It was first discovered that intestinal stem cells can reversely migrate in the crypt

Nature—— [69.504]

① Use cell lineage tracing and intravital microscopy techniques in mice, combined with mathematical modeling and in vitro experiments, to explore the behavior of LGR5+ stem cells in the small intestine and large intestine; ② Although there are similar LGR5+ in the crypts of the small intestine and large intestine Cell number and distribution, but the number of effective stem cells (can form long-term cell clone ) in the crypts of the small intestine is 2 times that of the large intestine; ③ This is due to the existence of Wnt-dependent (Paneth cells in the small intestine may be important Source) retrograde cell movement allows LGR5+ cells at the edge of the crypt to return to the bottom of the crypt, while there is almost no such retrograde movement in large intestine ; ④ This may explain why small intestinal crypts have more effective cells than large intestinal crypts Stem cells, slower monoclonal drift and faster LGR5+ cell regeneration.

[Editor’s comment]

Nature recently published a study conducted by scientists from many European countries. Based on in vivo microscopy and other research methods, it was discovered that there is a unique intestinal stem cell movement pattern in the small intestine—from the edge of the crypt to the bottom of the crypt. The center undergoes active reverse migration to counteract the conveyor-belt pattern of movement from the crypt to the villus tip and the resulting expulsion of stem cells from the stem cell nest. This pattern of cell motility is absent in large intestinal crypts. This allows the small intestine to have more effective stem cells than the large intestine, and monoclonal drift caused by the expansion of a single stem cell is slower and less common in the small intestine. These findings reveal a completely new cellular behavior of intestinal stem cells, providing new insights into stem cell regulation and physiological and disease differences between the small and large intestines (such as why cancer is more common in the large intestine but not the small intestine) . (@mildbreeze)

[Original information]

Retrograde movements determine effective stem cell numbers in the intestine

2022-07-13, doi: 10.1038/s41586-022-04962-0


Li Junhua + Xiao MinfengCell sub-issue: Understanding the human intestinal virome in one article Progress and Challenges of Cataloging (Review)

Cell Host and Microbe——[31.316]

① Based on 4 published enterovirome databases, it was found that the number of phages increased with the increase in sample size, indicating that the current database viral diversity has not reached saturation; ② There are limitations in identifying ssDNA, ssRNA and dsRNA phages based on viral metagenomic sequencing; ③ The cataloged virome database includes five steps: short reADs assembly, viral contig identification, quality assessment, annotation and bacterial host assignment; ④ Over 50% of enteroviruses The corresponding family cannot be annotated through the database, which is expected to be solved based on genome or gene clustering; ⑤ The four databases use the alignment dependence method to allocate hosts, and the interval database size and alignment parameters will affect the host prediction performance.

[Editor’s comment]

The human enterovirus group, often referred to as the “dark matter” of the intestinal microbiota, remains understudied. In recent years, with the development of sequencing technology and bioinformatics, large-scale human enterovirome studies have greatly improved people's understanding of the composition and variation of the enterovirome. With the establishment of the relevant human enterovirome database, it not only enriches the diversity and functional potential of enterovirus genomes, but also provides a reference database for related enterovirome research. However, there are still large differences in the methods and parameters used between different databases. Recently, Li Junhua, Xiao Minfeng and their team from the Shenzhen BGI Institute of Life Sciences published a latest review in Cell Host and Microbe, which included four recently published enterovirome databases (GVD, CHVD, MGV and GPD) and found the number of identified phages. This increased with increasing sample size, indicating that enterovirus diversity has not yet reached saturation in the current database.In addition, the authors summarize the five major steps for cataloging the human enterovirome database, as well as the challenges in phage taxonomic annotation and host assignment, and suggest that a wider and more diverse sample needs to be included in the future, which should be vigorously developed for viruses. A dedicated toolkit for group analysis and phage-host dynamic interactions, which is worthy of careful reading and careful review by relevant personnel. (@九青成)

[Original information]

Advances and challenges in cataloging the human gut virome

2022-07-13, doi: 10.1016/j.chom.2022.06.003


New progress in intestinal flora and mental health (review)

Molecular Psychiatry——[13.437]

① Specific intestinal flora may have a causal relationship with anxiety, anhedonia, depression, autism , neurodegenerative diseases and other mental diseases and treatment responses; ② The flora can pass through the vagus nerve pathway , hypothalamic-pituitary-adrenal axis, inflammation and immunity, and enteroendocrine cells affect the nervous system ; ③ Bacteria and metabolites can regulate autophagy and the endocannabinoid system through new pathways, as well as multiple pathways Interaction affects brain-gut interaction; ④ External exposure and internal factors can affect the microbiota, and disease can be improved by intervening with the microbiota to affect the brain-gut axis; ⑤ Microbiota-brain research is still in its infancy, and longitudinal population cohort studies will continue to be promoted field development.

[Editor's comment]

This is a review article published in Molecular Psychiatry. The author mainly summarizes the new progress in research related to intestinal flora and mental diseases, mainly including the causal relationship between specific intestinal flora and a series of mental diseases, and the new mechanism of the currently identified bacterial flora participating in the brain-gut axis interaction. , the ways in which environment/genetics, etc. influence the structure of the bacterial flora, how to intervene in the bacterial flora to improve clinical outcomes, and the knowledge barriers and challenges that still exist. (@Johnson)

[Original information]

The gut microbiome and mental health: advances in research and emerging priorities

2022-03-02, doi: 10.1038/s41380-022-01479-w


Domestic team: New surface-modified selenium nanoparticles may be Treatment of neuroinflammation

ACS Applied Materials & Interfaces——[10.383]

① Using chitosan (CS) and blood-brain barrier targeting peptide (Tg) to gradually modify the natural polyphenol dihydromyricetin (DMY)-coated nano-selenium particles (SeNPs) to obtain Tg-CS/DMY@SeNPs; ② Tg-CS/DMY@SeNPs can cross the blood-brain barrier, inhibit the aggregation of in the brains of APP/PS1 mice through the NF-κB pathway, and reduce the release of inflammatory cytokines. secretion; ③ Tg-CS/DMY@SeNPs can repair the intestinal barrier and regulate inflammation-related intestinal flora, such as Bifidobacterium, Dubois and Desulfovibrio; ④ Tg-CS/DMY@SeNPs can increase the expression of Gordonibacter The relative abundance of and downregulates the protein expression of NLRP3 inflammasome and the concentration of serum inflammatory factors.

[Editor's comment]

Neuroinflammation plays a key role in Alzheimer's disease (AD). However, it is unknown whether selenium nanoparticles (SeNPs) with different surface modifications can effectively treat neuroinflammation. The team of Zheng Guodong of Jiangxi Agricultural University and the team of Fuzhou University Yang Licong recently published an article in ACS Applied Materials & Interfaces, using chitosan (CS) and blood-brain barrier targeting peptide (Tg) to gradually modify the natural polyphenol dihydroarbutus Using DMY-coated selenium nanoparticles (SeNPs), new multifunctional nano-selenium particles Tg-CS/DMY@SeNPs with different surface modifications were obtained, and the new nano-selenium particles can pass through the intestinal flora-NLRP3 The inflammasome-brain axis improves neuroinflammation. Therefore, this new type of selenium nanoparticles can serve as an ideal candidate drug for the treatment of AD.(@元儿)

[Original information]

Multifunctional Selenium Nanoparticles with Different Surface Modifications Ameliorate Neuroinflammation through the Gut Microbiota-NLRP3 Inflammasome-Brain Axis in APP/PS1 Mice

2022-06-27, doi: 10.1021/acsami.2c06283


bifid bacilli in Prioritization effects of community assembly in human milk oligosaccharides

ISME Journal——[11.217]

① The metabolism of human milk oligosaccharides (HMOs) by four Bifidobacterium infantis was evaluated through individual culture, paired culture, and co-culture of four strains. Characteristics and community composition; ② In vitro experiments show that inoculation order and sugar consumption phenotype significantly affect community formation; ③ B. bifidum and B. infantis have strong utilization of HMO, and B. breve has limited HMO utilization, but only it can utilize HMO The downstream products fucose , they dominate the community through priority effects; ④ The abundance of B. breve in the fecal metagenome of breast-fed infants is consistent with the trend in in vitro experiments; ⑤ The importance and historical dependence of the initial community combination on the infant intestine The mature contribution of tract flora is greater.

[Editor’s comment]

This is a work published in ISME. Through genome prediction and in vitro culture experiments, the author revealed the community of Bifidobacterium infantis under conditions using human milk oligosaccharides (HMO) as a substrate. Assembly features. Among them, the priority effect contributes greatly to community assembly. Bifidobacterium bifidum and Bifidobacterium infantis have strong utilization of HMO, and Bifidobacterium breve can exclusively monopolize fucose, the downstream product of HMO, for proliferation. Breastfed infant fecal metagenomic data also showed higher abundance of Bifidobacterium breve. (@Johnson)

[Original information]

Priority effects shape the structure of infant-type Bifidobacterium communities on human milk oligosaccharides

2022-06-29, doi: 10.1038/s41396-022-01270-3


Bacteroides thetaiotaomicron may treat alcoholism Liver disease

Gut Microbes——[9.434]

① Alcohol treatment of mice can lead to a decrease in the abundance of Bacteroides thetaiotaomicron (Bt) in their intestines, while Bt supplementation can maintain its abundance, improve hepatic steatosis, and reduce glycerol Triester content; ② Bt promotes the production of mucin2 by increasing mucus thickness, inhibiting the phosphorylation of MMP9, ERK and Notch signaling, thereby restoring the intestinal mucosal barrier function and reducing the production of LPS; ③ In addition, Bt can upregulate GLP-1, Downregulates the expression of FGF15 induced by ethanol, thereby regulating bile acid metabolism; ④ Bt can restore phosphorylation of AMPK, reduce SREBP-1c levels, inhibit fatty acid synthesis, while improving mitochondrial adaptability and function, and ultimately improve liver lipid metabolism. .

[Editor’s comment]

Intestinal flora plays a key role in alcohol-related liver disease (ALD), and Bacteroides thetaiotaomicron (Bt) is an important member of the intestinal flora and plays a role in metabolism, intestinal immunity, and mucosal barrier. Plays an important role, but its role in the development of ethanol-induced hepatic steatosis is unknown. A recent article published in Gut Microbe shows that oral Bt can restore intestinal barrier function by increasing mucus thickness, while improving and improving liver lipid metabolism by regulating bile acid metabolism, ultimately alleviating experimental ALD. Therefore, Bt may be used as a new probiotic for the treatment of ALD.(@元儿)

【Original information】

Recovery of Bacteroides thetaiotaomicron ameliorates hepatic steatosis in experimental alcohol-related liver disease

2022-07-03, doi: 10.1080/19490976.2022.2089006


iMeta: Bacteria for parasitic plants columns are used as ( Orobanche cumana) parasitism

iMeta——[N/A]

① In this study, the author investigated the rhizosphere soil flora of sunflower with different degrees of parasitism; ② According to the different degrees of parasitism, there are significant differences in the microbial structure, among which the yellow Monadaceae was enriched in severe parasitism; ③ Metagenomic analysis showed that amino acids , carbohydrates , energy and lipid metabolism were increased in the rhizosphere soil of severely infected sunflowers; ④ Cyclo (Pro-Val ) was identified as an active metabolite of strain HX79, and metabolomics and molecular docking methods confirmed that it can promote sunflower seed germination and growth; ⑤ The author also found that Pseudomonas Montesori HX1 inhibits sunflower seed germination and growth When grown in host rhizosphere soil.

[Editor's comment]

This article studies the biological control of the root parasitic weed Orobanche cumana, and proposes that the bacterial community structure affects Orobanche cumana. Based on the functional analysis of the bacterial community and the prediction of biomarkers, it is found that Two strains of bacteria can significantly change the number of host root series and their chemical regulation mechanisms were studied. The results of this study elucidate the regulatory effect of rhizosphere microbiota on the parasitic plant Helianthus annua and may help develop a new weed suppression strategy. (@Liu Yongxin - Chinese Academy of Sciences - metagenome)

[Original information]

Microbial community roles and chemical mechanisms in the parasitic development of Orobanche cumana

2022-06-13, doi: 10.1002/imt2.31


Thanks to the creator of this daily newspaper: mildbreeze , Jiu Qingchen, Akkk, DMG-Quasimodo, Paihuabaobao, WK Hongye, Liu Yongxin-Chinese Academy of Sciences-Metagenomic

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