Dataset Information

Fecal microbial transplantation and a high fiber diet attenuates emphysema development by suppressing inflammation and apoptosis.

ABSTRACT: Recent work has suggested a microbial dysbiosis association between the lung and gut in respiratory diseases. Here, we demonstrated that gut microbiome modulation attenuated emphysema development. To modulate the gut microbiome, fecal microbiota transplantation (FMT) and diet modification were adopted in mice exposed to smoking and poly I:C for the emphysema model. We analyzed the severity of emphysema by the mean linear intercept (MLI) and apoptosis by the fluorescent TUNEL assay. Microbiome analysis was also performed in feces and fecal extracellular vesicles (EVs). The MLI was significantly increased with smoking exposure. FMT or a high-fiber diet (HFD) attenuated the increase. Weight loss, combined with smoking exposure, was not noted in mice with FMT. HFD significantly decreased macrophages and lymphocytes in bronchoalveolar lavage fluid. Furthermore, IL-6 and IFN-γ were decreased in the bronchoalveolar lavage fluid and serum. The TUNEL score was significantly lower in mice with FMT or HFD, suggesting decreased cell apoptosis. In the microbiome analysis, Bacteroidaceae and Lachnospiraceae, which are alleged to metabolize fiber into short-chain fatty acids (SCFAs), increased at the family level with FMT and HFD. FMT and HFD attenuated emphysema development via local and systemic inhibition of inflammation and changes in gut microbiota composition, which could provide a new paradigm in COPD treatment.

SUBMITTER: Jang YO

PROVIDER: S-EPMC8080776 | biostudies-literature | 2020 Jul

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Fecal microbial transplantation and a high fiber diet attenuates emphysema development by suppressing inflammation and apoptosis.

Jang Yoon Ok YO Lee Se Hee SH Choi Jong Jin JJ Kim Do-Hyun DH Choi Je-Min JM Kang Min-Jong MJ Oh Yeon-Mok YM Park Young-Jun YJ Shin Yong Y Lee Sei Won SW

Experimental & molecular medicine 20200717 7

Recent work has suggested a microbial dysbiosis association between the lung and gut in respiratory diseases. Here, we demonstrated that gut microbiome modulation attenuated emphysema development. To modulate the gut microbiome, fecal microbiota transplantation (FMT) and diet modification were adopted in mice exposed to smoking and poly I:C for the emphysema model. We analyzed the severity of emphysema by the mean linear intercept (MLI) and apoptosis by the fluorescent TUNEL assay. Microbiome an ...[more]

PMID: 32681029

Similar Datasets

Project description:BackgroundRetinoid X receptors (RXRs) are members of the nuclear receptor (NR) superfamily that mediate signalling by 9-cis retinoic acid, a vitamin A derivative. RXRs play key roles not only as homodimers but also as heterodimeric partners, e.g., for retinoic acid receptors, vitamin D receptors, and peroxisome proliferator-activated receptors. The NR family may also play important roles in the development of emphysema. However, the role of RXRs in the pathogenesis of emphysema is not well defined.MethodsWe developed a novel RXR partial agonist (NEt-4IB) and investigated its effect and mechanism compared to a full agonist (bexarotene) in a murine model of emphysema. For emphysema induction, BALB/c mice received intraperitoneal cigarette smoke extract (CSE) or intratracheal porcine pancreas elastase (PPE). Treatment with RXR agonists was initiated before or after emphysema induction.ResultsTreatment with NEt-4IB significantly suppressed the increase in static lung compliance and emphysematous changes in CSE-induced emphysema and PPE-induced established and progressive emphysema. NEt-4IB significantly suppressed PPE-induced neutrophilic airway inflammation and the levels of keratinocyte chemoattractant (KC), C-X-C motif ligand5 (CXCL5), interferon (IFN)-γ and IL-17. NEt-4IB also improved the matrix metalloproteinase-9 (MMP-9)/tissue inhibitor of metalloproteinase-1 (TIMP-1) imbalance and the reduced anti-oxidant activity in bronchoalveolar lavage (BAL) fluid. NEt-4IB suppressed PPE-induced vascular endothelial growth factor (VEGF) expression in the airway. Treatment with NEt-4IB and bexarotene significantly suppressed the increase in static lung compliance and emphysematous changes. However, adverse effects of RXR agonists, including hypertriglyceridemia and hepatomegaly, were observed in bexarotene-treated mice but not in NEt-4IB-treated mice.ConclusionThese data suggest that RXRs play crucial roles in emphysema and airway inflammation, and novel partial RXR agonists could be potential therapeutic strategies for the treatment of PPE- and CSE-induced emphysema.

Project description:Growing evidence of fecal microbiota transplantation (FMT) and fecal virus transplantation (FVT) provides a possibility to regulate animal health, whereas little is known about the impact of the 2 methods. This study aimed to investigate the effects of gut microbes on jejunal function in healthy broiler chickens, with the objective of establishing a theoretical basis for the application of FMT and FVT. Cecal feces from 28-day-old AA broilers were collected to prepare gavage juice for FMT and FVT. FMT for Group FM, FVT for group FV and PBS gavage for group CON, continuously treated for 6 days start at 5-day-old chicks. Samples were collected at d 11 and d 21. The results showed that the treatment d 2 and the overall fecal score in treatment groups were significantly lower than CON group (P < 0.05). The jejunum morphology showed that FMT increased crypt depth, decreased villus height, V/C (P < 0.05) and FVT increased villus height (P < 0.05) at d 11. At d 21, villus height and crypt depth significantly higher (P < 0.05) in group FM and group FV. The expression of Claudin1, Occludin, ZO2, and Muc2 in the FV group was significantly increased (P < 0.05) at 11-day-old. FMT increased the secretion of sIgA at 11-day-old, and this influence lasted up to 21-day-old (P < 0.05). At 11-day-old, the expression of b0+AT of basic amino acid transport carrier and chymotrypsin activity (P < 0.05) had a significant correlation. At 21 d of age, FVT significantly increased the expression of PepT1 and SGLT1 (P < 0.05). At 11-day-old, FM group showed significantly higher faith pd index (P = 0.004) and Shannon index (P = 0.037), and separated from FV and CON according to PCoA. Among differentiating bacteria, Bacteroides significantly enriched (P < 0.05) in group FM, which positively correlated with the expression of ZO2, Muc2, Occludin, and Claudin1; R_Ruminococcus, L_Ruminococcus, Butyricicoccuss significantly enriched (P < 0.05) in group CON, which significantly higher than processing groups, R_Ruminococcus and L_Ruminococcus negatively correlated with the expression of Occludin (P < 0.05), and R_Ruminococcus, Butyricicoccus negatively correlated with the expression of Claudin1 (P < 0.05). At 21-day-old, PCoA based on Bray-Curtis shows that microbes taxa of 3 groups are isolated with each other and treatment groups were significant different with CON group based on Unweighted UniFrac and weighted UniFrac. The expression of PepT1 was significantly negatively (P < 0.05) correlated with Ruminococcus, and the expression of sIgA was significantly negatively (P < 0.05) correlated with Parabacteroides. In conclusion, FMT regulated intestinal flora rapidly, while it had little effect on intestinal function and a higher potential damaging risk on jejunal. FVT regulated intestinal flora structure softer, improved tight junction expression, but the mechanism of action needs further exploration.

Dataset Information

Fecal microbial transplantation and a high fiber diet attenuates emphysema development by suppressing inflammation and apoptosis.

Publications

Fecal microbial transplantation and a high fiber diet attenuates emphysema development by suppressing inflammation and apoptosis.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets