The Microbiota-Gut-Brain Axis

Physiological Reviews, Journal Year: 2019, Volume and Issue: 99(4), P. 1877 - 2013

Published: Aug. 28, 2019

The importance of the gut-brain axis in maintaining homeostasis has long been appreciated. However, past 15 yr have seen emergence microbiota (the trillions microorganisms within and on our bodies) as one key regulators function led to appreciation a distinct microbiota-gut-brain axis. This is gaining ever more traction fields investigating biological physiological basis psychiatric, neurodevelopmental, age-related, neurodegenerative disorders. brain communicate with each other via various routes including immune system, tryptophan metabolism, vagus nerve enteric nervous involving microbial metabolites such short-chain fatty acids, branched chain amino peptidoglycans. Many factors can influence composition early life, infection, mode birth delivery, use antibiotic medications, nature nutritional provision, environmental stressors, host genetics. At extreme diversity diminishes aging. Stress, particular, significantly impact at all stages life. Much recent work implicated gut many conditions autism, anxiety, obesity, schizophrenia, Parkinson’s disease, Alzheimer’s disease. Animal models paramount linking regulation fundamental neural processes, neurogenesis myelination, microbiome activation microglia. Moreover, translational human studies are ongoing will greatly enhance field. Future focus understanding mechanisms underlying attempt elucidate microbial-based intervention therapeutic strategies for neuropsychiatric

Language: Английский

---

Clostridium species as probiotics: potentials and challenges

Journal of Animal Science and Biotechnology/Journal of animal science and biotechnology, Journal Year: 2020, Volume and Issue: 11(1)

Published: Feb. 20, 2020

Abstract Clostridium species, as a predominant cluster of commensal bacteria in our gut, exert lots salutary effects on intestinal homeostasis. Up to now, species have been reported attenuate inflammation and allergic diseases effectively owing their distinctive biological activities. Their cellular components metabolites, like butyrate, secondary bile acids indolepropionic acid, play probiotic role primarily through energizing epithelial cells, strengthening barrier interacting with immune system. In turn, diets physical state body can shape unique pattern gut. view performances, huge potential probiotics. However, there are still some nonnegligible risks challenges approaching application them. Given this, this review summarized the researches involved benefits health, order develop novel probiotics for human health animal production.

Language: Английский

---

Tumor metastasis to lymph nodes requires YAP-dependent metabolic adaptation

Science, Journal Year: 2019, Volume and Issue: 363(6427), P. 644 - 649

Published: Feb. 8, 2019

Fueling lymph node metastases Metastatic cells can migrate from a primary tumor to distant organs through two routes: They enter the bloodstream directly, or they adjacent tumor. Little is known about biological mechanisms that allow survive and grow within nodes. Studying mouse models, Lee et al. found adapt microenvironment by shifting their metabolism toward fatty acid oxidation. This occurs activation of signaling pathway driven yes-associated protein (YAP) transcription factor. Importantly, inhibition oxidation YAP suppressed metastasis in mice. Science , this issue p. 644

Language: Английский

---

Molecular physiology of bile acid signaling in health, disease, and aging

Physiological Reviews, Journal Year: 2020, Volume and Issue: 101(2), P. 683 - 731

Published: Aug. 13, 2020

Several diseases and conditions have been associated with an uncontrolled rise in bile acid (BA) concentrations. This is often the case when tight feedback regulation of BA synthesis compromised to point that BAs become detrimental. their cognate receptors, farnesoid X receptor (FXR) Takeda G-protein 5 (TGR5), however, exert many beneficial roles as they enable tissues adapt environmental, nutritional, physiological cues. Over last two decades, mimetics targeting FXR, TGR5, or both, proven be efficacious alleviating chronic metabolic inflammatory disorders, such obesity, Type 2 diabetes (T2D), atherosclerosis non-alcoholic steatohepatitis (NASH). While several aspects signaling are still poorly understood, first therapeutics FXR making way into clinic treat liver diseases, primary biliary cholangitis (PBC) NASH. Drugs may, hence, a bright future continuing efforts on studying impact changing pathways humans will translate our emerging knowledge physiology model organisms clinical benefits.

Language: Английский

---

The Role of Enterobacteriaceae in Gut Microbiota Dysbiosis in Inflammatory Bowel Diseases

Microorganisms, Journal Year: 2021, Volume and Issue: 9(4), P. 697 - 697

Published: March 27, 2021

Inflammatory bowel diseases (IBDs) are a group of chronic gastrointestinal inflammatory with unknown etiology. There is combination well documented factors in their pathogenesis, including intestinal microbiota dysbiosis. The symbiotic plays important functions the host, and loss beneficial microbes could favor expansion microbial pathobionts. In particular, bloom potentially harmful Proteobacteria, especially Enterobacteriaceae, has been described as enhancing response, observed IBDs. Herein, we seek to investigate contribution Enterobacteriaceae IBD pathogenesis whilst considering continuous literature data. Despite mechanism still remaining unclear, be correlated increase nitrate oxygen levels inflamed gut bile acid dysmetabolism patients. Furthermore, several studies conducted at species level, it suggested that some adherent-invasive Escherichia coli (AIEC) play an role pathogenesis. Overall, this review highlights pivotal played by dysbiosis associated progression.

Language: Английский

---

Intestinal Permeability, Inflammation and the Role of Nutrients

Nutrients, Journal Year: 2020, Volume and Issue: 12(4), P. 1185 - 1185

Published: April 23, 2020

The interaction between host and external environment mainly occurs in the gastrointestinal tract, where mucosal barrier has a critical role many physiologic functions ranging from digestion, absorption, metabolism. This allows passage absorption of nutrients, but at same time, it must regulate contact luminal antigens immune system, confining undesirable products to lumen. Diet is an important regulator barrier, cross-talk among dietary factors, microbiota crucial for modulation intestinal permeability maintenance tract (GI) homeostasis. In present review, we will discuss number nutrients that have been proposed as regulators inflammation epithelial function. We also consider metabolic function microbiota, which capable elaborating diverse synthesizing great interest. Better knowledge influence on can be future development new therapeutic approaches patients with dysfunction, factor pathogenesis GI non-GI diseases.

Language: Английский

---

Intestinal Bacteria Interplay With Bile and Cholesterol Metabolism: Implications on Host Physiology

Frontiers in Physiology, Journal Year: 2019, Volume and Issue: 10

Published: March 14, 2019

Bile is a biological fluid synthesized in the liver, mainly constituted by bile acids and cholesterol, which functions as detergent that emulsifies solubilizes lipids, thereby playing an essential role fat digestion. Besides, are important signaling molecules regulate key at intestinal systemic levels human body, affecting glucose lipid metabolism, immune homeostasis. Apart from this, due to their amphipathic nature, toxic for bacterial cells and, thus, exert strong selective pressure on microbial populations inhabiting gut, decisively shaping profiles of our gut microbiota, has been recognized metabolic organ pivotal host health. Remarkably, bacteria also display range enzymatic activities capable acting lesser extent, cholesterol. These can have direct impact physiology they influence composition circulating acid pool host, Given changes microbiota-residing biotransformation ability significantly health status. Elucidating ways fine-tune microbiota-bile acids-host interplay promising strategies act cholesterol-related disorders. This manuscript summarizes current knowledge cholesterol metabolism bacteria, well its physiology, identifying gaps opportunities guide further advances field.

Language: Английский

---

A human-origin probiotic cocktail ameliorates aging-related leaky gut and inflammation via modulating the microbiota/taurine/tight junction axis

JCI Insight, Journal Year: 2020, Volume and Issue: 5(9)

Published: April 17, 2020

Inflammation is a major risk factor of morbidity and mortality in older adults. Although its precise etiology unknown, low-grade inflammation adults commonly associated with increased intestinal epithelial permeability (leaky gut) abnormal (dysbiotic) gut microbiota. The increasing population lack treatments to reduce aging-related microbiota dysbiosis, leaky gut, culminates rise comorbidities, constituting significant public health concern. Here, we demonstrate that human-origin probiotic cocktail containing 5 Lactobacillus Enterococcus strains isolated from healthy infant prevented high-fat diet–induced (HFD-induced) inflammation, metabolic dysfunctions, physical function decline mice. Probiotic-modulated primarily reduced by tight junctions, which turn inflammation. Mechanistically, probiotics modulated way increase bile salt hydrolase activity, taurine abundance the stimulated junctions suppressed leakiness. Furthermore, Caenorhabditis elegans, life span, adiposity enhanced function. results suggest such therapies could prevent or treat elderly.

Language: Английский

---

Metabolic Messengers: bile acids

Nature Metabolism, Journal Year: 2022, Volume and Issue: 4(4), P. 416 - 423

Published: March 25, 2022

Language: Английский

---

Odevixibat treatment in progressive familial intrahepatic cholestasis: a randomised, placebo-controlled, phase 3 trial

˜The œLancet. Gastroenterology & hepatology, Journal Year: 2022, Volume and Issue: 7(9), P. 830 - 842

Published: July 1, 2022

Progressive familial intrahepatic cholestasis (PFIC) is a group of inherited paediatric liver diseases resulting from mutations in genes that impact bile secretion. We aimed to evaluate the effects odevixibat, an ileal acid transporter inhibitor, versus placebo children with PFIC.Patients eligible for this 24-week, randomised, double-blind, completed, phase 3 study were outpatients diagnosed PFIC1 or PFIC2 who had pruritus and elevated serum acids at screening. Patients randomly assigned (1:1:1) using interactive web-based system once day oral placebo, odevixibat 40 μg/kg, 120 μg/kg. Randomisation was done block size six stratified by PFIC type patient age; patients, clinicians, staff blinded treatment allocation. enrolled one 33 global sites. Two primary endpoints evaluated: proportion positive assessments (PPAs; ie, scratching score ≤1 ≥1-point decrease as assessed caregivers Albireo observer-reported outcome [ObsRO] PRUCISION instrument) over 24 weeks, patients response (ie, reduced ≥70% baseline concentrations ≤70 μmol/L) week 24. Efficacy safety analysed allocated received more doses drug. This registered ClinicalTrials.gov, NCT03566238.Between June 21, 2018, Feb 10, 2020, 62 (median age 3·2 [range 0·5-15·9] years) (n=20), μg/kg per (n=23), (n=19). Model-adjusted (least squares) mean PPAs significantly higher (55% [SE 8] combined [58% 52% group] vs 30% 9] group; model-adjusted difference 25·0% [95% CI 8·5-41·5]; p=0·0038). The percentage also (14 [33%] 42 [10 four none 20 adjusting stratification factor [PFIC type], 30·7% 12·6-48·8; p=0·0030]). most common treatment-emergent adverse events (TEAEs) diarrhoea frequent bowel movements (13 [31%] two [10%] placebo) fever (12 [29%] five [25%] 20); serious TEAEs occurred three (7%) odevixibat-treated (25%) placebo-treated patients.In PFIC, effectively generally well tolerated. Odevixibat, administered capsules, non-surgical, pharmacological option interrupt enterohepatic circulation PFIC.Albireo Pharma.

Language: Английский

---