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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 -
Cell Jun 2018The ketogenic diet (KD) is used to treat refractory epilepsy, but the mechanisms underlying its neuroprotective effects remain unclear. Here, we show that the gut...
The ketogenic diet (KD) is used to treat refractory epilepsy, but the mechanisms underlying its neuroprotective effects remain unclear. Here, we show that the gut microbiota is altered by the KD and required for protection against acute electrically induced seizures and spontaneous tonic-clonic seizures in two mouse models. Mice treated with antibiotics or reared germ free are resistant to KD-mediated seizure protection. Enrichment of, and gnotobiotic co-colonization with, KD-associated Akkermansia and Parabacteroides restores seizure protection. Moreover, transplantation of the KD gut microbiota and treatment with Akkermansia and Parabacteroides each confer seizure protection to mice fed a control diet. Alterations in colonic lumenal, serum, and hippocampal metabolomic profiles correlate with seizure protection, including reductions in systemic gamma-glutamylated amino acids and elevated hippocampal GABA/glutamate levels. Bacterial cross-feeding decreases gamma-glutamyltranspeptidase activity, and inhibiting gamma-glutamylation promotes seizure protection in vivo. Overall, this study reveals that the gut microbiota modulates host metabolism and seizure susceptibility in mice.
Topics: Animals; Anti-Bacterial Agents; Bacteroides; Diet, Ketogenic; Disease Models, Animal; Feces; Gastrointestinal Microbiome; Glutamic Acid; Hippocampus; Intestinal Mucosa; Kv1.1 Potassium Channel; Metabolome; Mice; Mice, Inbred C3H; Mice, Knockout; Principal Component Analysis; RNA, Ribosomal, 16S; Seizures; gamma-Aminobutyric Acid; gamma-Glutamyltransferase
PubMed: 29804833
DOI: 10.1016/j.cell.2018.04.027 -
Cell Host & Microbe Feb 2024Gene-environment interactions shape behavior and susceptibility to depression. However, little is known about the signaling pathways integrating genetic and...
Gene-environment interactions shape behavior and susceptibility to depression. However, little is known about the signaling pathways integrating genetic and environmental inputs to impact neurobehavioral outcomes. We report that gut G-protein-coupled receptor, Gpr35, engages a microbe-to-brain metabolic pathway to modulate neuronal plasticity and depressive behavior in mice. Psychological stress decreases intestinal epithelial Gpr35, genetic deletion of which induces depressive-like behavior in a microbiome-dependent manner. Gpr35 mice and individuals with depression have increased Parabacteroides distasonis, and its colonization to wild-type mice induces depression. Gpr35 and Parabacteroides distasonis-colonized mice show reduced indole-3-carboxaldehyde (IAld) and increased indole-3-lactate (ILA), which are produced from opposing branches along the bacterial catabolic pathway of tryptophan. IAld and ILA counteractively modulate neuroplasticity in the nucleus accumbens, a brain region linked to depression. IAld supplementation produces anti-depressant effects in mice with stress or gut epithelial Gpr35 deficiency. Together, these findings elucidate a gut microbe-brain signaling mechanism that underlies susceptibility to depression.
Topics: Animals; Mice; Bacteroidetes; Brain; Gastrointestinal Microbiome; Microbiota
PubMed: 38198925
DOI: 10.1016/j.chom.2023.12.009 -
Cell Metabolism Oct 2023Non-alcoholic fatty liver disease (NAFLD) is regarded as a pandemic that affects about a quarter of the global population. Recently, host-gut microbiota metabolic...
Non-alcoholic fatty liver disease (NAFLD) is regarded as a pandemic that affects about a quarter of the global population. Recently, host-gut microbiota metabolic interactions have emerged as distinct mechanistic pathways implicated in the development of NAFLD. Here, we report that a group of gut microbiota-modified bile acids (BAs), hyodeoxycholic acid (HDCA) species, are negatively correlated with the presence and severity of NAFLD. HDCA treatment has been shown to alleviate NAFLD in multiple mouse models by inhibiting intestinal farnesoid X receptor (FXR) and upregulating hepatic CYP7B1. Additionally, HDCA significantly increased abundances of probiotic species such as Parabacteroides distasonis, which enhances lipid catabolism through fatty acid-hepatic peroxisome proliferator-activated receptor alpha (PPARα) signaling, which in turn upregulates hepatic FXR. These findings suggest that HDCA has therapeutic potential for treating NAFLD, with a unique mechanism of simultaneously activating hepatic CYP7B1 and PPARα.
Topics: Mice; Animals; Non-alcoholic Fatty Liver Disease; PPAR alpha; Liver; Deoxycholic Acid; Bile Acids and Salts
PubMed: 37591244
DOI: 10.1016/j.cmet.2023.07.011 -
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 -
Nature Communications Apr 2022Calorie restriction (CR) and fasting are common approaches to weight reduction, but the maintenance is difficult after resuming food consumption. Meanwhile, the gut...
Calorie restriction (CR) and fasting are common approaches to weight reduction, but the maintenance is difficult after resuming food consumption. Meanwhile, the gut microbiome associated with energy harvest alters dramatically in response to nutrient deprivation. Here, we reported that CR and high-fat diet (HFD) both remodeled the gut microbiota with similar microbial composition, Parabacteroides distasonis was most significantly decreased after CR or HFD. CR altered microbiota and reprogramed metabolism, resulting in a distinct serum bile acid profile characterized by depleting the proportion of non-12α-hydroxylated bile acids, ursodeoxycholic acid and lithocholic acid. Downregulation of UCP1 expression in brown adipose tissue and decreased serum GLP-1 were observed in the weight-rebound mice. Moreover, treatment with Parabacteroides distasonis or non-12α-hydroxylated bile acids ameliorated weight regain via increased thermogenesis. Our results highlighted the gut microbiota-bile acid crosstalk in rebound weight gain and Parabacteroides distasonis as a potential probiotic to prevent rapid post-CR weight gain.
Topics: Animals; Bacteroidetes; Bile Acids and Salts; Caloric Restriction; Diet, High-Fat; Gastrointestinal Microbiome; Mice; Mice, Inbred C57BL; Weight Gain
PubMed: 35440584
DOI: 10.1038/s41467-022-29589-7 -
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 -
International Journal of Molecular... Nov 2022There is a growing body of evidence highlighting there are significant changes in the gut microbiota composition and relative abundance in various neurological... (Review)
Review
There is a growing body of evidence highlighting there are significant changes in the gut microbiota composition and relative abundance in various neurological disorders. We performed a systematic review of the different microbiota altered in a wide range of neurological disorders (Alzheimer's disease (AD), Parkinson's disease (PD), multiple sclerosis (MS), amyotrophic lateral sclerosis, and stroke). Fifty-two studies were included representing 5496 patients. At the genus level, the most frequently involved microbiota are Akkermansia, Faecalibacterium, and Prevotella. The overlap between the pathologies was strongest for MS and PD, sharing eight genera (Akkermansia, Butyricicoccus, Bifidobacterium, Coprococcus, Dorea, Faecalibacterium, Parabacteroides, and Prevotella) and PD and stroke, sharing six genera (Enterococcus, Faecalibacterium, Lactobacillus, Parabacteroides, Prevotella, and Roseburia). The identification signatures overlapping for AD, PD, and MS raise the question of whether these reflect a common etiology or rather common consequence of these diseases. The interpretation is hampered by the low number and low power for AD, ALS, and stroke with ample opportunity for false positive and false negative findings.
Topics: Humans; Gastrointestinal Microbiome; Nervous System Diseases; Parkinson Disease; Microbiota; Akkermansia; Multiple Sclerosis; Prevotella; Clostridiaceae; Clostridiales; Stroke
PubMed: 36430144
DOI: 10.3390/ijms232213665 -
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