Effect of Synbiotics on Amelioration of Intestinal Inflammation Under Hypobaric Hypoxia

Khanna Kunjan; Mishra Kamla Prasad; Chanda Sudipta; Ganju Lilly; Singh Shashi Bala; Kumar Bhuvnesh

摘要

Khanna, Kunjan, Kamla Prasad Mishra, Sudipta Chanda, Lilly Ganju, Shashi Bala Singh, and Bhuvnesh Kumar. Effect of synbiotics on amelioration of intestinal inflammation under hypobaric hypoxia. High Alt Med Biol. 00:000-000, 2020.Aim: High-altitude exposure alters the gastrointestinal (GI) system, which may be a cause of hypobaric hypoxia (HH)-induced microbial dysbiosis. Therefore, we investigated the effect of a combination of beneficial bacteria and nondigestible fiber popularly known as "synbiotics" (Syn) to mitigate intestinal inflammation and microbial dysbiosis post-HH exposure.Methods: Syn, that is, a combination of probiotics and prebiotics, was given to male Sprague-Dawley rats 3 days prior and along with the HH exposure to assess its effect on mucosal barrier injury and inflammation. Changes in the gut microbiota and functional analysis were assessed using 16S rRNA and whole-genome sequencing (WGS) analysis.Results: Syn treatment significantly improved mucosal barrier injury in terms of decreased serum fluorescein isothiocyanate dextran from 96.1 +/- 7.95 mu g/ml in HH-alone group to 38.35 +/- 4.55 mu g/ml in HH + Syn group (p 0.01) and decreased serum zonulin levels, that is, from 134.7 +/- 19.05 ng/ml (HH alone) to 64.02 +/- 7.33 ng/ml (HH + Syn) (p 0.05), along with improvement in the intestinal villi under HH exposure. Levels of proinflammatory cytokines and chemokines significantly reduced upon Syn treatment, indicating attenuation of inflammation and immune cell migration. Syn treatment significantly reduced Th17 biased immune response preventing interleukin (IL)-17-induced inflammatory response with 8.1 +/- 0.5 ng/mg protein in HH exposure group, while treatment with Syn in HH-exposed group reduced IL-17 levels to 2.01 +/- 0.3 ng/mg protein (p 0.001). Analysis of 16S rRNA showed significant (p 0.05) alterations in Deferribacteres, Firmicutes, and Verrucomicrobia at the phylum levels, whereas Prevotella, Paenibacillus, Clostridium, Turicibacter, Bacillus, Anoxybacillus, Enterococcus, SMB53, Mucispirillum, Allobaculum, and Lactococcus were significantly altered (p 0.05) in abundance at the genus level. WGS analysis revealed improvement in GI health by regulating functional pathways post-Syn treatment.Conclusion: Our findings indicate that Syn treatment improves intestinal barrier function and curtailed inflammation in the HH-exposed rat models, proving it to be a promising potential countermeasure for HH-induced gut problems.

机译：Khanna，Kunjan，Kamla Prasad Mishra，Sudipta Chanda，Lilly Ganju，Shashi Bala Singh和Bhuvnesh Kumar。同步对低氧缺氧下肠炎改善的影响。高Alt Med Biol。 00：000-000,2020.aim：高空曝光改变了胃肠道（GI）系统，这可能是低次数缺氧（HH）引起的微生物脱泻病的原因。因此，我们研究了有益细菌和非易性纤维的组合伴随着称为“同步性”（Synbiotics“（Syn）的影响，以减轻肠炎症和微生物脱泻后的HH暴露。方法：SYN，即益生菌和益生元组合， 3天之前给予雄性Sprague-Dawley大鼠，以及HH暴露，评估其对粘膜阻隔损伤和炎症的影响。使用16S rRNA和全基因组测序（WGS）分析评估肠道微生物群和功能分析的变化。结果：SYN处理在96.1 +/-7.95μmg/ ml下降的血清荧光素异硫氰酸酯葡聚糖的粘膜阻隔损伤显着改善在HH-LOP组中以38.35 +/- 4.55mM g / ml在HH + SYN组（P <0.01）中，降低血清Zonulin水平，即从134.7 +/- 19.05 ng / ml（单独）至64.02 + / - 7.33 ng / ml（HH + SYN）（P <0.05），以及HH暴露下的肠绒毛的改善。在合并处理后，促炎细胞因子和趋化因子的水平显着降低，表明炎症和免疫细胞迁移的衰减。 SYN治疗显着降低了TH17偏置免疫应答，防止白细胞介素（IL）-17诱导的HH暴露组中的8.1 +/- 0.5ng / mg蛋白质的炎症反应，同时用HH-暴露的组中的SYN处理将IL-17水平降至2.01 +/- 0.3 ng / mg蛋白质（p <0.001）。 16S rRNA的分析显示出延长的杆菌，压延和疣状病症的显着（P <0.05）改变，而PREVOTALLA，Pavotella，Paenibacillus，Clostridium，Turicibacter，Bacillus，anoxybacillus，肠球菌，SMB53，Mucirululum，Allobaculum和乳乳杆菌被显着改变（P <0.05）在属级别的丰富。 WGS分析揭示了通过SYN治疗功能途径进行了改善的GI健康。结论：我们的研究结果表明，SYN治疗改善了HH-暴露大鼠模型中的肠道屏障功能和缩减炎症，证明了其对HH的有希望的潜在对策诱导肠道问题。

Effect of Synbiotics on Amelioration of Intestinal Inflammation Under Hypobaric Hypoxia

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