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FEMS Microbiology Letters Aug 2022The stability of gut microbiota is essential for the host's health. Parabacteroides spp., core members of the human gut microbiota, have an average abundance of 1.27% in... (Review)
Review
The stability of gut microbiota is essential for the host's health. Parabacteroides spp., core members of the human gut microbiota, have an average abundance of 1.27% in humans of 12 populations. Parabacteroides have recently been reported to have a close relationship with host health (e.g. metabolic syndrome, inflammatory bowel disease and obesity). Parabacteroides have the physiological characteristics of carbohydrate metabolism and secreting short chain fatty acids. However, antimicrobial resistance of Parabacteroides to antibiotics (such as clindamycin, moxifloxacin and cefoxitin) should not be ignored. In this review, we primarily focus on Parabacteroides distasonis, Parabacteroides goldsteinii, Parabacteroides johnsonii and Parabacteroides merdae and discuss their relationships with host disease, diet and the prevention or induction of diseases. Pa. distasonis and Pa. goldsteinii may be viewed as potential next generation probiotic candidates due to their protective effects on inflammation and obesity in mice. We also discuss the potential therapeutic application of Parabacteroides spp. in maintaining host-intestine homeostasis.
Topics: Animals; Bacteroides; Gastrointestinal Microbiome; Humans; Intestines; Mice; Obesity; Probiotics
PubMed: 35945336
DOI: 10.1093/femsle/fnac072 -
Gut Sep 2023Gut microbiota dysbiosis is closely linked to the pathogenesis of rheumatoid arthritis (RA). We aimed to identify potential probiotic gut microbes that can ameliorate...
OBJECTIVE
Gut microbiota dysbiosis is closely linked to the pathogenesis of rheumatoid arthritis (RA). We aimed to identify potential probiotic gut microbes that can ameliorate the development of RA.
DESIGN
Microbiota profiling in patients with RA and healthy individuals was investigated via 16S rDNA bacterial gene sequencing and shotgun metagenomics. Collagen-induced arthritic mice and TNF-α transgenic mice were used to evaluate the roles of the gut commensal in RA. The effects of -derived microbial metabolites on the differentiation of CD4 T cells and macrophage polarisation were also investigated.
RESULTS
The relative abundance of in new-onset patients with RA and patients with RA with history of the disease was downregulated and this decrease was negatively correlated with Disease Activity Score-28 (DAS28). Oral treatment of arthritic mice with live (LPD) considerably ameliorated RA pathogenesis. LPD-derived lithocholic acid (LCA), deoxycholic acid (DCA), isolithocholic acid (isoLCA) and 3-oxolithocholic acid (3-oxoLCA) had similar and synergistic effects on the treatment of RA. In addition to directly inhibiting the differentiation of Th17 cells, 3-oxoLCA and isoLCA were identified as TGR5 agonists that promoted the M2 polarisation of macrophages. A specific synthetic inhibitor of bile salt hydrolase attenuated the antiarthritic effects of LPD by reducing the production of these four bile acids. The natural product ginsenoside Rg2 exhibited its anti-RA effects by promoting the growth of .
CONCLUSIONS
and ginsenoside Rg2 might represent probiotic and prebiotic agents in the treatment of RA.
Topics: Mice; Animals; Arthritis, Rheumatoid; Bacteroidetes; Bacteria
PubMed: 36604114
DOI: 10.1136/gutjnl-2022-327756 -
Nature Microbiology Aug 2023Non-alcoholic steatohepatitis (NASH) is the severe form of non-alcoholic fatty liver disease, and is characterized by liver inflammation and fat accumulation. Dietary...
Non-alcoholic steatohepatitis (NASH) is the severe form of non-alcoholic fatty liver disease, and is characterized by liver inflammation and fat accumulation. Dietary interventions, such as fibre, have been shown to alleviate this metabolic disorder in mice via the gut microbiota. Here, we investigated the mechanistic role of the gut microbiota in ameliorating NASH via dietary fibre in mice. Soluble fibre inulin was found to be more effective than insoluble fibre cellulose to suppress NASH progression in mice, as shown by reduced hepatic steatosis, necro-inflammation, ballooning and fibrosis. We employed stable isotope probing to trace the incorporation of C-inulin into gut bacterial genomes and metabolites during NASH progression. Shotgun metagenome sequencing revealed that the commensal Parabacteroides distasonis was enriched by C-inulin. Integration of C-inulin metagenomes and metabolomes suggested that P. distasonis used inulin to produce pentadecanoic acid, an odd-chain fatty acid, which was confirmed in vitro and in germ-free mice. P. distasonis or pentadecanoic acid was protective against NASH in mice. Mechanistically, inulin, P. distasonis or pentadecanoic acid restored gut barrier function in NASH models, which reduced serum lipopolysaccharide and liver pro-inflammatory cytokine expression. Overall this shows that gut microbiota members can use dietary fibre to generate beneficial metabolites to suppress metabolic disease.
Topics: Animals; Mice; Non-alcoholic Fatty Liver Disease; Inulin; Fatty Acids; Inflammation; Dietary Fiber
PubMed: 37386075
DOI: 10.1038/s41564-023-01418-7 -
Gut Microbes 2021is the type strain for the genus , a group of gram-negative anaerobic bacteria that commonly colonize the gastrointestinal tract of numerous species. First isolated in... (Review)
Review
is the type strain for the genus , a group of gram-negative anaerobic bacteria that commonly colonize the gastrointestinal tract of numerous species. First isolated in the 1930s from a clinical specimen as , the strain was re-classified to form the new genus in 2006. Currently, the genus consists of 15 species, 10 of which are listed as 'validly named' (, and ) and 5 'not validly named' (, and ) by the List of Prokaryotic names with Standing in Nomenclature. The genus has been associated with reports of both beneficial and pathogenic effects in human health. Herein, we review the literature on the history, ecology, diseases, antimicrobial resistance, and genetics of this bacterium, illustrating the effects of on human and animal health.
Topics: Animals; Anti-Bacterial Agents; Bacteroidetes; Drug Resistance, Bacterial; Gastrointestinal Microbiome; Gram-Negative Bacterial Infections; Humans; Phylogeny; Probiotics
PubMed: 34196581
DOI: 10.1080/19490976.2021.1922241 -
Gut Feb 2022Chronic obstructive pulmonary disease (COPD) is a global disease characterised by chronic obstruction of lung airflow interfering with normal breathing. Although the...
OBJECTIVE
Chronic obstructive pulmonary disease (COPD) is a global disease characterised by chronic obstruction of lung airflow interfering with normal breathing. Although the microbiota of respiratory tract is established to be associated with COPD, the causality of gut microbiota in COPD development is not yet established. We aimed to address the connection between gut microbiota composition and lung COPD development, and characterise bacteria and their derived active components for COPD amelioration.
DESIGN
A murine cigarette smoking (CS)-based model of COPD and strategies evaluating causal effects of microbiota were performed. Gut microbiota structure was analysed, followed by isolation of target bacterium. Single cell RNA sequencing, together with sera metabolomics analyses were performed to identify host responsive molecules. Bacteria derived active component was isolated, followed by functional assays.
RESULTS
Gut microbiota composition significantly affects CS-induced COPD development, and faecal microbiota transplantation restores COPD pathogenesis. A commensal bacterium was isolated and shown to ameliorate COPD. Reduction of intestinal inflammation and enhancement of cellular mitochondrial and ribosomal activities in colon, systematic restoration of aberrant host amino acids metabolism in sera, and inhibition of lung inflammations act as the important COPD ameliorative mechanisms. Besides, the lipopolysaccharide derived from is anti-inflammatory, and significantly ameliorates COPD by acting as an antagonist of toll-like receptor 4 signalling pathway.
CONCLUSION
The gut microbiota-lung COPD axis was connected. A potentially benefial bacterial strain and its functional component may be developed and used as alternative agents for COPD prevention or treatment.
Topics: Animals; Bacteroidetes; Disease Models, Animal; Fecal Microbiota Transplantation; Gastrointestinal Microbiome; Lipopolysaccharides; Mice; Mice, Inbred C57BL; Pulmonary Disease, Chronic Obstructive; Smoking
PubMed: 33687943
DOI: 10.1136/gutjnl-2020-322599 -
Nature Communications Apr 2023Parabacteroides distasonis (P. distasonis) plays an important role in human health, including diabetes, colorectal cancer and inflammatory bowel disease. Here, we show...
Parabacteroides distasonis (P. distasonis) plays an important role in human health, including diabetes, colorectal cancer and inflammatory bowel disease. Here, we show that P. distasonis is decreased in patients with hepatic fibrosis, and that administration of P. distasonis to male mice improves thioacetamide (TAA)- and methionine and choline-deficient (MCD) diet-induced hepatic fibrosis. Administration of P. distasonis also leads to increased bile salt hydrolase (BSH) activity, inhibition of intestinal farnesoid X receptor (FXR) signaling and decreased taurochenodeoxycholic acid (TCDCA) levels in liver. TCDCA produces toxicity in mouse primary hepatic cells (HSCs) and induces mitochondrial permeability transition (MPT) and Caspase-11 pyroptosis in mice. The decrease of TCDCA by P. distasonis improves activation of HSCs through decreasing MPT-Caspase-11 pyroptosis in hepatocytes. Celastrol, a compound reported to increase P. distasonis abundance in mice, promotes the growth of P. distasonis with concomitant enhancement of bile acid excretion and improvement of hepatic fibrosis in male mice. These data suggest that supplementation of P. distasonis may be a promising means to ameliorate hepatic fibrosis.
Topics: Humans; Mice; Male; Animals; Pyroptosis; Liver Cirrhosis; Liver; Hepatocytes; Bile Acids and Salts; Caspases; Mice, Inbred C57BL
PubMed: 37005411
DOI: 10.1038/s41467-023-37459-z -
Nature Metabolism Oct 2022Obesity, dyslipidemia and gut dysbiosis are all linked to cardiovascular diseases. A Ganoderma meroterpene derivative (GMD) has been shown to alleviate obesity and...
Obesity, dyslipidemia and gut dysbiosis are all linked to cardiovascular diseases. A Ganoderma meroterpene derivative (GMD) has been shown to alleviate obesity and hyperlipidemia through modulating the gut microbiota in obese mice. Here we show that GMD protects against obesity-associated atherosclerosis by increasing the abundance of Parabacteroides merdae in the gut and enhancing branched-chain amino acid (BCAA) catabolism. Administration of live P. merdae to high-fat-diet-fed ApoE-null male mice reduces atherosclerotic lesions and enhances intestinal BCAA degradation. The degradation of BCAAs is mediated by the porA gene expressed in P. merdae. Deletion of porA from P. merdae blunts its capacity to degrade BCAAs and leads to inefficacy in fighting against atherosclerosis. We further show that P. merdae inhibits the mTORC1 pathway in atherosclerotic plaques. In support of our preclinical findings, an in silico analysis of human gut metagenomic studies indicates that P. merdae and porA genes are depleted in the gut microbiomes of individuals with atherosclerosis. Our results provide mechanistic insights into the therapeutic potential of GMD through P. merdae in treating obesity-associated cardiovascular diseases.
Topics: Humans; Mice; Animals; Male; Cardiovascular Diseases; Amino Acids, Branched-Chain; Bacteroides; Obesity; Mice, Obese; Mechanistic Target of Rapamycin Complex 1; Atherosclerosis; Apolipoproteins E
PubMed: 36253620
DOI: 10.1038/s42255-022-00649-y -
Cell Reports Jan 2019We demonstrated the metabolic benefits of Parabacteroides distasonis (PD) on decreasing weight gain, hyperglycemia, and hepatic steatosis in ob/ob and high-fat diet...
We demonstrated the metabolic benefits of Parabacteroides distasonis (PD) on decreasing weight gain, hyperglycemia, and hepatic steatosis in ob/ob and high-fat diet (HFD)-fed mice. Treatment with live P. distasonis (LPD) dramatically altered the bile acid profile with elevated lithocholic acid (LCA) and ursodeoxycholic acid (UDCA) and increased the level of succinate in the gut. In vitro cultivation of PD demonstrated its capacity to transform bile acids and production of succinate. Succinate supplementation in the diet decreased hyperglycemia in ob/ob mice via the activation of intestinal gluconeogenesis (IGN). Gavage with a mixture of LCA and UDCA reduced hyperlipidemia by activating the FXR pathway and repairing gut barrier integrity. Co-treatment with succinate and LCA/UDCA mirrored the benefits of LPD. The binding target of succinate was identified as fructose-1,6-bisphosphatase, the rate-limiting enzyme in IGN. The succinate and secondary bile acids produced by P. distasonis played key roles in the modulation of host metabolism.
Topics: Animals; Bacterial Proteins; Bacteroidetes; Bile Acids and Salts; Gastrointestinal Microbiome; Humans; Mice; Obesity; Succinic Acid
PubMed: 30605678
DOI: 10.1016/j.celrep.2018.12.028 -
Nature Communications Nov 2023Gut microbiota plays a key role in insulin resistance (IR). Here we perform a case-control study of Chinese adults (ChiCTR2200065715) and identify that Parabacteroides...
Gut microbiota plays a key role in insulin resistance (IR). Here we perform a case-control study of Chinese adults (ChiCTR2200065715) and identify that Parabacteroides distasonis is inversely correlated with IR. Treatment with P. distasonis improves IR, strengthens intestinal integrity, and reduces systemic inflammation in mice. We further demonstrate that P. distasonis-derived nicotinic acid (NA) is a vital bioactive molecule that fortifies intestinal barrier function via activating intestinal G-protein-coupled receptor 109a (GPR109a), leading to ameliorating IR. We also conduct a bioactive dietary fiber screening to induce P. distasonis growth. Dendrobium officinale polysaccharide (DOP) shows favorable growth-promoting effects on P. distasonis and protects against IR in mice simultaneously. Finally, the reduced P. distasonis and NA levels were also validated in another human type 2 diabetes mellitus cohort. These findings reveal the unique mechanisms of P. distasonis on IR and provide viable strategies for the treatment and prevention of IR by bioactive dietary fiber.
Topics: Animals; Humans; Mice; Case-Control Studies; Diabetes Mellitus, Type 2; Dietary Fiber; Insulin Resistance
PubMed: 38007572
DOI: 10.1038/s41467-023-43622-3 -
Gut Feb 2019The medicinal fungus and its anamorph have a long history of use in traditional Chinese medicine for their immunomodulatory properties. Alterations of the gut...
OBJECTIVE
The medicinal fungus and its anamorph have a long history of use in traditional Chinese medicine for their immunomodulatory properties. Alterations of the gut microbiota have been described in obesity and type 2 diabetes. We examined the possibility that mycelium (HSM) and isolated fractions containing polysaccharides may prevent diet-induced obesity and type 2 diabetes by modulating the composition of the gut microbiota.
DESIGN
High-fat diet (HFD)-fed mice were treated with HSM or fractions containing polysaccharides of different molecular weights. The effects of HSM and polysaccharides on the gut microbiota were assessed by horizontal faecal microbiota transplantation (FMT), antibiotic treatment and 16S rDNA-based microbiota analysis.
RESULTS
Fraction H1 containing high-molecular weight polysaccharides (>300 kDa) considerably reduced body weight gain (∼50% reduction) and metabolic disorders in HFD-fed mice. These effects were associated with increased expression of thermogenesis protein markers in adipose tissues, enhanced gut integrity, reduced intestinal and systemic inflammation and improved insulin sensitivity and lipid metabolism. Gut microbiota analysis revealed that H1 polysaccharides selectively promoted the growth of , a commensal bacterium whose level was reduced in HFD-fed mice. FMT combined with antibiotic treatment showed that neomycin-sensitive gut bacteria negatively correlated with obesity traits and were required for H1's anti-obesogenic effects. Notably, oral treatment of HFD-fed mice with live reduced obesity and was associated with increased adipose tissue thermogenesis, enhanced intestinal integrity and reduced levels of inflammation and insulin resistance.
CONCLUSIONS
HSM polysaccharides and the gut bacterium represent novel prebiotics and probiotics that may be used to treat obesity and type 2 diabetes.
Topics: Animals; Ascomycota; Bacteroidetes; Diabetes Mellitus, Type 2; Diet, High-Fat; Fecal Microbiota Transplantation; Fungal Polysaccharides; Gastrointestinal Microbiome; Insulin Resistance; Male; Mice; Mice, Inbred C57BL; Molecular Weight; Obesity; Prebiotics; Symbiosis
PubMed: 30007918
DOI: 10.1136/gutjnl-2017-315458