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 Parabacteroides distasonis in RA. The effects of P. distasonis -derived microbial metabolites on the differentiation of CD4 ⁺ T cells and macrophage polarisation were also investigated. Results: The relative abundance of P. distasonis 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 P. distasonis (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 P. distasonis . Conclusions: P. distasonis and ginsenoside Rg2 might represent probiotic and prebiotic agents in the treatment of RA.

Exhausted-like CD8 ⁺ resident memory T cells in the lung limit immune activation–driven fibrosis.

Atherosclerosis (AS) is exacerbated in the perimenopausal period, which significantly increases the incidence rate of cardiovascular disease. The disruption of the gut microbiota has been associated with AS or menopause, but the specific changes of AS-associated gut microbiota in the perimenopausal period remain largely unknown. As lipid abnormalities are mainly responsible for AS, the relationship between lipid metabolism abnormalities and gut microbiota disruptions during menopause is rarely reported hitherto. In the present study, ApoE^−/- mice fed with a high-fat diet (HFD) were subjected to ovariectomy and supplemented with estrogen. The ovariectomized HFD-fed ApoE^−/- mice underwent significant AS damage, hepatic lipid damage, hyperlipidemia, and changes of lipid metabolism- and transport-related enzymes. There was significantly higher abundance of some lipid metabolites in the plasma of ovariectomized HFD-fed ApoE^−/- mice than in non-ovariectomized ones, including cholesterol esters, triglycerides, phospholipids, and other types of lipids (free fatty acids, acylcarnitine, sphingomyelins, and ceramides). The administration of estrogen significantly reduced the contents of most lipid metabolites. The diversity and composition of gut microbiota evidently changed in ovariectomized HFD-fed ApoE^−/- mice, compared to HFD-fed ApoE^−/- mice without ovariectomy. In contrast, with estrogen supplementation, the diversity and composition of gut microbiota were restored to approach that of non-ovariectomized HFD-fed ApoE^−/- mice, and the relative abundances of some bacteria were even like those of C57BL/6 mice fed with a normal diet. On the other hand, the transplantation of feces from C57BL/6 mice fed with normal diet to ovariectomized HFD-fed ApoE^−/- mice was sufficient to correct the hyperlipidemia and AS damage, and to reverse the characteristics changing of lipid metabolomics in ovariectomized HFD-fed ApoE^−/- mice. These phenomena were also been observed after transplantation of feces from estrogen-treated ovariectomized HFD-fed ApoE^−/- mice to ovariectomized HFD-fed ApoE^−/- mice. Moreover, the gut microbiota and lipid metabolites were significantly correlated, demonstrating that the changes of serum lipids may be associated with the gut microbiota disruptions in the perimenopausal period. In conclusion, the gut microbiota during the progression of AS in the perimenopausal period showed specific compositional changes and significant correlations with circulating lipid metabolites. Estrogen supplementation may exert beneficial effects on gut bacteria and lipid metabolism.

Respiratory syncytial virus (RSV) is a leading viral pathogen responsible for lower respiratory tract infections, particularly in children under five years worldwide, often resulting in hospitalization. At present, the molecular-level interactions between RSV and its host and the underlying mechanisms of RSV-induced inflammation are poorly understood. Herein, we describe an untargeted high-resolution lipidomics platform based on UHPLC-Q-Exactive-MS to assess the lipid alterations of lung tissues and plasma from a mouse model of RSV pneumonia. Untargeted lipidomics using LC-MS with multivariate analysis was applied to describe the lipidomic profiling of the lung tissues and plasma in RSV pneumonia mice. Lipid identification was conducted via an in silico MS/MS LipidBlast library using the MS-DIAL software. We observed distinct compartmental lipid signatures in the mice lung tissues and plasma and significant lipid profile changes between the systematic and localized host responses to RSV. A total of 87 and 68 differential lipids were captured in the mice lung tissue and plasma, respectively, including phospholipids, sphingolipids, acylcarnitine, and fatty acids. Some of these lipids belong to pulmonary surfactants, illustrating that RSV pneumonia-induced aberrations of the pulmonary surfactant system may play a vital role in the etiology of respiratory inflammation. Our findings reveal that the host responses to RSV and various lipid metabolic pathways were linked to disease pathology. Furthermore, our findings could provide mechanistic insights into RSV pneumonia.

The Zushima tablet (ZT) has been used for decades in the clinical treatment of rheumatoid arthritis (RA) in China. However, its therapeutic mechanism is unclear. In this study, we aimed to explore the distinctive metabolic patterns in collagen-induced arthritis (CIA) rats and evaluate the therapeutic effects of ZT on RA using untargeted serum and fecal metabolomics approaches based on gas chromatography coupled with mass spectrometry. Body weight, hind paw swelling, TNF-α and IL-1β levels, arthritis scores, and histopathological parameters were assessed. In the metabolomics study, 31 altered metabolites in the serum and 30 in the feces were identified by comparing the model with the control group using statistical processing. These altered metabolites revealed that the tricarboxylic acid cycle, glycolysis metabolism, fatty acid metabolism, and purine metabolism were disturbed in CIA rats, and most of these altered metabolites including l-isoleucine, l-aspartic acid, pyruvic acid, cholic acid, and hypoxanthine, were rectified by ZT. Furthermore, short-chain fatty acids in feces were quantitatively determined, and the results showed that ZT could regulate the levels of propionate, butyrate, and valerate in CIA rats. Then, gut microbiota were analyzed by 16S rRNA analysis. Our results showed that Firmicutes and Bacteroidetes were the most abundant bacteria in rats. The levels of 19 types of bacteria at the family level were altered in RA rats, and most of them could be regulated by ZT. This study demonstrated that metabolomics analysis is a powerful tool for providing novel insight into RA and for elucidating the potential mechanism of ZT.