Protective Role of Colitis in Inflammatory Arthritis via Propionate-Producing Bacteroides in the Gut

OBJECTIVES: To investigate whether and how inflammatory disease in the intestine influences the development of arthritis, considering that organ-to-organ communication is associated with many physiological and pathological events. METHODS: First, mice were given drinking water containing dextran sodium sulfate (DSS) and then subjected to inflammatory arthritis. We compared the phenotypic symptoms between the cohoused and separately-housed mice. Next, donor mice were divided into DSS-treated and untreated groups and then cohoused with recipient mice. Arthritis was then induced in the recipients. The fecal microbiome was analyzed by 16S rRNA amplicon sequencing. We obtained type strains of the candidate bacteria and generated propionate-deficient mutant bacteria. Short-chain fatty acids were measured in the bacterial culture supernatant, serum, feces, and cecum contents using gas chromatography-mass spectrometry. Mice fed with candidate and mutant bacteria were subjected to inflammatory arthritis. RESULTS: Contrary to expectations, the mice treated with DSS exhibited fewer symptoms of inflammatory arthritis. Intriguingly, the gut microbiota contributes, at least in part, to the improvement of colitis-mediated arthritis. Among the altered microorganisms, CONCLUSIONS: We suggest a novel relationship between the gut and joints and an important role of the gut microbiota as communicators. Moreover, the propionate-producin

Elevated IFNA1 and suppressed IL12p40 associated with persistent hyperinflammation in COVID-19 pneumonia

IntroductionDespite of massive endeavors to characterize inflammation in COVID-19 patients, the core network of inflammatory mediators responsible for severe pneumonia stillremain remains elusive. MethodsHere, we performed quantitative and kinetic analysis of 191 inflammatory factors in 955 plasma samples from 80 normal controls (sample n = 80) and 347 confirmed COVID-19 pneumonia patients (sample n = 875), including 8 deceased patients. ResultsDifferential expression analysis showed that 76% of plasmaproteins (145 factors) were upregulated in severe COVID-19 patients comparedwith moderate patients, confirming overt inflammatory responses in severe COVID-19 pneumonia patients. Global correlation analysis of the plasma factorsrevealed two core inflammatory modules, core I and II, comprising mainly myeloid cell and lymphoid cell compartments, respectively, with enhanced impact in a severity-dependent manner. We observed elevated IFNA1 and suppressed IL12p40, presenting a robust inverse correlation in severe patients, which was strongly associated with persistent hyperinflammation in 8.3% of moderate pneumonia patients and 59.4% of severe patients. DiscussionAberrant persistence of pulmonary and systemic inflammation might be associated with long COVID-19 sequelae. Our comprehensive analysis of inflammatory mediators in plasmarevealed the complexity of pneumonic inflammation in COVID-19 patients anddefined critical modules responsible for severe pneumonic progression

Identification of Biochemical Differences in White and Brown Adipocytes Using FTIR Spectroscopy

This study was conducted to investigate the developmental characteristics of adipocytes and to identify selectively white and brown adipocytes through Fourier transform infrared (FTIR) spectroscopy. For the developmental characterization of adipocytes, cells and conditioned media of white and brown adipocytes were respectively collected and analyzed. A higher amide I/amide II ratio was observed in the conditioned medium of brown adipocyte than in that of white adipocyte, indicating differences in secretory protein profiles. In contrast, an amide I/amide II ratio was higher in white adipocytes than in brown adipocytes, and mature adipocytes have higher lipid amounts than pre-adipocytes. Lipid acyl chain length was the longest in white adipocytes. These differences suggested that FTIR spectroscopy can be used to characterize developmental stages and/or types of adipocytes. To identify the possibility of selectively classifying adipose-derived stem cells, FTIR spectroscopy spectra were obtained in cells before/after white/brown adipocyte differentiation using FTIR spectroscopy and then analyzed by the principal component analysis method. All data indicated that the discrimination between adipocytes was possible in the analysis of the infrared spectroscopy spectrum by the principal component analysis technique. This study suggested the possibility of FTIR spectroscopy as a new type of cell sorting system without tagging

Protective role of colitis in inflammatory arthritis via propionate-producing Bacteroides in the gut

ObjectivesTo investigate whether and how inflammatory disease in the intestine influences the development of arthritis, considering that organ-to-organ communication is associated with many physiological and pathological events. MethodsFirst, mice were given drinking water containing dextran sodium sulfate (DSS) and then subjected to inflammatory arthritis. We compared the phenotypic symptoms between the cohoused and separately-housed mice. Next, donor mice were divided into DSS-treated and untreated groups and then cohoused with recipient mice. Arthritis was then induced in the recipients. The fecal microbiome was analyzed by 16S rRNA amplicon sequencing. We obtained type strains of the candidate bacteria and generated propionate-deficient mutant bacteria. Short-chain fatty acids were measured in the bacterial culture supernatant, serum, feces, and cecum contents using gas chromatography-mass spectrometry. Mice fed with candidate and mutant bacteria were subjected to inflammatory arthritis. ResultsContrary to expectations, the mice treated with DSS exhibited fewer symptoms of inflammatory arthritis. Intriguingly, the gut microbiota contributes, at least in part, to the improvement of colitis-mediated arthritis. Among the altered microorganisms, Bacteroides vulgatus and its higher taxonomic ranks were enriched in the DSS-treated mice. B. vulgatus, B. caccae, and B. thetaiotaomicron exerted anti-arthritic effects. Propionate production deficiency further prevented the protective effect of B. thetaiotaomicron on arthritis. ConclusionsWe suggest a novel relationship between the gut and joints and an important role of the gut microbiota as communicators. Moreover, the propionate-producing Bacteroides species examined in this study may be a potential candidate for developing effective treatments for inflammatory arthritis.Y

DataSheet_1_Protective role of colitis in inflammatory arthritis via propionate-producing Bacteroides in the gut.pdf

ObjectivesTo investigate whether and how inflammatory disease in the intestine influences the development of arthritis, considering that organ-to-organ communication is associated with many physiological and pathological events.MethodsFirst, mice were given drinking water containing dextran sodium sulfate (DSS) and then subjected to inflammatory arthritis. We compared the phenotypic symptoms between the cohoused and separately-housed mice. Next, donor mice were divided into DSS-treated and untreated groups and then cohoused with recipient mice. Arthritis was then induced in the recipients. The fecal microbiome was analyzed by 16S rRNA amplicon sequencing. We obtained type strains of the candidate bacteria and generated propionate-deficient mutant bacteria. Short-chain fatty acids were measured in the bacterial culture supernatant, serum, feces, and cecum contents using gas chromatography-mass spectrometry. Mice fed with candidate and mutant bacteria were subjected to inflammatory arthritis.ResultsContrary to expectations, the mice treated with DSS exhibited fewer symptoms of inflammatory arthritis. Intriguingly, the gut microbiota contributes, at least in part, to the improvement of colitis-mediated arthritis. Among the altered microorganisms, Bacteroides vulgatus and its higher taxonomic ranks were enriched in the DSS-treated mice. B. vulgatus, B. caccae, and B. thetaiotaomicron exerted anti-arthritic effects. Propionate production deficiency further prevented the protective effect of B. thetaiotaomicron on arthritis.ConclusionsWe suggest a novel relationship between the gut and joints and an important role of the gut microbiota as communicators. Moreover, the propionate-producing Bacteroides species examined in this study may be a potential candidate for developing effective treatments for inflammatory arthritis.</p