The microbiome and gut homeostasis

Science, Journal Year: 2022, Volume and Issue: 377(6601)

Published: June 30, 2022

Changes in the composition of gut microbiota are associated with many human diseases. So far, however, we have failed to define homeostasis or dysbiosis by presence absence specific microbial species. The and function adult is governed diet host factors that regulate direct growth. delivers oxygen nitrate lumen small intestine, which selects for bacteria use respiration energy production. In colon, contrast, limits availability nitrate, results a bacterial community specializes fermentation Although influences composition, poor weakens control mechanisms microbiota. Hence, quantifying parameters growth could help offer alternative strategies remediate dysbiosis.

Language: Английский

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Intestinal transgene delivery with native E. coli chassis allows persistent physiological changes

Cell, Journal Year: 2022, Volume and Issue: 185(17), P. 3263 - 3277.e15

Published: Aug. 1, 2022

Live bacterial therapeutics (LBTs) could reverse diseases by engrafting in the gut and providing persistent beneficial functions host. However, attempts to functionally manipulate microbiome of conventionally raised (CR) hosts have been unsuccessful because engineered microbial organisms (i.e., chassis) difficulty colonizing hostile luminal environment. In this proof-of-concept study, we use native bacteria as chassis for transgene delivery impact CR host physiology. Native Escherichia coli isolated from stool cultures mice were modified express functional genes. The reintroduction these strains induces perpetual engraftment intestine. addition, E. can induce changes that affect physiology pathology months after administration. Thus, using "knock in" specific allows mechanistic studies activities enables LBT with curative intent.

Language: Английский

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Interactive Relationships between Intestinal Flora and Bile Acids

International Journal of Molecular Sciences, Journal Year: 2022, Volume and Issue: 23(15), P. 8343 - 8343

Published: July 28, 2022

The digestive tract is replete with complex and diverse microbial communities that are important for the regulation of multiple pathophysiological processes in humans animals, particularly those involved maintenance intestinal homeostasis, immunity, inflammation, tumorigenesis. diversity bile acids a result joint efforts host microflora. There bidirectional relationship between community that, while flora tightly modulates metabolism synthesis acids, acid pool composition affect homeostasis flora. Homeostatic imbalances systems may lead to development variety diseases, such as inflammatory bowel disease (IBD), colorectal cancer (CRC), hepatocellular carcinoma (HCC), type 2 diabetes (T2DM), polycystic ovary syndrome (PCOS). interactions be (in)directly pathogenesis these diseases.

Language: Английский

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Rosmarinic Acid Restores Colonic Mucus Secretion in Colitis Mice by Regulating Gut Microbiota-Derived Metabolites and the Activation of Inflammasomes

Journal of Agricultural and Food Chemistry, Journal Year: 2023, Volume and Issue: 71(11), P. 4571 - 4585

Published: March 8, 2023

Maintaining a steady state of mucus barrier is an important potential target for polyphenol to exert its anticolitis activity. This study elucidates the pivotal role rosmaric acid (RA) in regulating function and alleviating inflammation by identifying gut microbiota-derived metabolites evaluating inhibitory effect on inflammasomes colitis mice. Results demonstrated that RA treatment promoted proliferation goblet cells restored level secretion, especially Muc2. reshaped microbiota mice, particularly boost core probiotics, such as p. Bacteroidaceae, f. Muribaculaceae, g. Alistipes, Clostridia_UCG-014. Nontargeted metabonomics targeted confirmed significant increase bile acids their (7-sulfocholic acid, stercobilin, chenodeoxycholic 3-sulfate, sulfate, ursodeoxycholic 3-sulfate), indole ((R)-2,3-dihydro-3,5-dihydroxy-2-oxo-3-indoleacetic frovatriptan, 3-formyl-6-hydroxyindole, brassicanal A), short-chain fatty (SCFAs) (acetic butyric isobutyric isovaleric valeric acid) contributed strengthened function. In addition, being absorbed mainly lower digestive tract, inhibited overexpression (especially NLRP6) occurred mice promote secretion cells. These data RA, promising candidate enhance health, colonic mediating production inflammasomes. The presented provides scientific evidence explaining apparent paradox low bioavailability high bioactivity polyphenols.

Language: Английский

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High-Fat Diet-Induced Decreased Circulating Bile Acids Contribute to Obesity Associated with Gut Microbiota in Mice

Foods, Journal Year: 2024, Volume and Issue: 13(5), P. 699 - 699

Published: Feb. 25, 2024

The altered circulating bile acids (BAs) modulate gut microbiota, energy metabolism and various physiological functions. BA profiles in liver, serum, ileum feces of HFD-fed mice were analyzed with normal chow diet (NCD)-fed after 16-week feeding. Furthermore, microbiota was its correlation analysis performed. result showed that long-term HFD feeding significantly decreased hepatic serum levels, mainly attributed to the inhibition synthesis reduced reabsorption efficiency BAs enterohepatic circulation. It also impaired glucose lipid homeostasis mice. We found higher salt hydrolase activity ileal microbes a ratio free conjugated content contents groups compared NCD group mice, which might account for activated intestinal farnesoid X receptor signaling on liver reabsorption. associated dysregulation according TGR5 BAT. In addition, it is astonishing find extremely high percentages taurocholate 12-OH both groups, substrate selectivity transporter during This study revealed significant effect pool collectively resulted metabolic disorders obesity.

Language: Английский

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Safety and efficacy of elobixibat for chronic constipation: results from a randomised, double-blind, placebo-controlled, phase 3 trial and an open-label, single-arm, phase 3 trial

˜The œLancet. Gastroenterology & hepatology, Journal Year: 2018, Volume and Issue: 3(8), P. 537 - 547

Published: May 25, 2018

Language: Английский

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Pathogenicity and virulence of the liver flukesFasciola hepaticaandFasciolaGiganticathat cause the zoonosis Fasciolosis

Virulence, Journal Year: 2021, Volume and Issue: 12(1), P. 2839 - 2867

Published: Oct. 26, 2021

Fasciolosis caused by the liver flukes Fasciola hepatica and gigantica is one of most important neglected parasitic diseases humans animals. The ability parasites to infect multiply in their intermediate snail hosts, adaptation a wide variety mammalian definitive hosts contribute high transmissibility distribution. Within host, trauma immature burrowing through parenchyma associated with pathogenesis. Similarly, feeding activity physical presence large bile ducts can lead anemia, inflammation, obstruction cholangitis. frequency non-synonymous polymorphisms found spp. genes allows for invasion broad range hosts. This also facilitated parasite's excretory-secretory (ES) molecules that mediate physiological changes establishment within host. ES contains cathepsin peptidases aid parasite degrading collagen fibronectin. In ducts, cathepsin-L critical hemoglobin digestion during activities. Other (peroxiredoxin, Kunitz-type inhibitor) stimulate strong immune response polarized toward Treg/Th2 phenotype favors fluke's survival. Helminth defense molecule, fatty acid binding proteins, Fasciola-specific glycans miRNAs modulate host pro-inflammatory responses, while antioxidant scavenger enzymes work an orchestrated way deter oxidant-mediated damage. Combining these strategies survive decades where they reproduce spread become widespread zoonotic worm world.

Language: Английский

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Disturbances in Cholesterol Homeostasis and Non-alcoholic Fatty Liver Diseases

Frontiers in Medicine, Journal Year: 2020, Volume and Issue: 7

Published: Sept. 2, 2020

Non-alcoholic fatty liver disease (NAFLD) is a major health problem associated with obesity along other features of the metabolic syndrome including insulin resistance and dyslipidemia. The accumulation lipids in hepatocytes causes damage triggers inflammation, fibrosis cirrhosis. Beside acids triglycerides, evidence shows an increase free cholesterol subsequent toxic effects contributing to damage. maintenance homeostasis body requires balance between several pathways responsible for synthesis, transport conversion into bile acids. Intestinal absorption also one determinants homeostasis. nature changes NAFLD has been subject extensive investigations. In this article, we will attempt provide brief overview current knowledge about disturbances metabolism discuss how certain molecular targets these could be exploited treatment multifactorial disease.

Language: Английский

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Bile acids as inflammatory mediators and modulators of intestinal permeability

Frontiers in Immunology, Journal Year: 2022, Volume and Issue: 13

Published: Dec. 7, 2022

Bile acids are critical for the digestion and absorption of lipids fat-soluble vitamins; however, evidence continues to emerge supporting additional roles bile as signaling molecules. After they synthesized from cholesterol in liver, primary modified into secondary by gut flora contributing a diverse pool making composition highly sensitive alterations microbiota. Disturbances acid homeostasis have been observed patients with Inflammatory Bowel Diseases (IBD). In fact, decrease was shown occur because IBD-associated dysbiosis. Further, increase luminal due malabsorption Crohn's ileitis ileal resection has implicated induction diarrhea exacerbation inflammation. A causal link between intestinal inflammation recently suggested. With respect potential mechanisms related IBD, several studies provided strong direct effects on permeability porcine rodent models well humans. Interestingly, different were exert distinct inflammatory response that require careful consideration. Such findings revealed effect changes relative abundance development IBD. This review summarizes current knowledge about mediators modulators mainly context bowel diseases.

Language: Английский

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Intestinal secretory mechanisms and diarrhea

AJP Gastrointestinal and Liver Physiology, Journal Year: 2022, Volume and Issue: 322(4), P. G405 - G420

Published: Feb. 16, 2022

One of the primary functions intestinal epithelium is to transport fluid and electrolytes from luminal contents. Under normal circumstances, absorptive secretory processes are tightly regulated such that absorption predominates, thereby enabling conservation large volumes water pass through intestine each day. However, in conditions diarrhea, this balance becomes dysregulated, so secretion, driven primarily by Cl

Language: Английский

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