Obesity Worsens Gulf War Illness Symptom Persistence Pathology by Linking Altered Gut Microbiome Species to Long-Term Gastrointestinal, Hepatic, and Neuronal Inflammation in a Mouse Model.
Obesity Worsens Gulf War Illness Symptom Persistence Pathology by Linking Altered Gut Microbiome Species to Long-Term Gastrointestinal, Hepatic, and Neuronal Inflammation in a Mouse Model.
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DOI：
10.3390/nu12092764
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发表时间：
2020-09-10
期刊：
影响因子：
5.9
通讯作者：
Chatterjee S
中科院分区：
文献类型：
--
作者：
Bose D;Saha P;Mondal A;Fanelli B;Seth RK;Janulewicz P;Sullivan K;Lasley S;Horner R;Colwell RR;Shetty AK;Klimas N;Chatterjee S
海湾战争疾病（GWI）的病理持续部署的退伍军人是一个临床挑战，即使在近三十年后。最近的研究表明，海湾战争退伍军人中肥胖和代谢紊乱的患病率较高，主要是由于创伤后应激障碍（PTSD）、慢性疲劳、久坐不动的生活方式和高碳水化合物/高脂肪饮食的存在。我们验证了这样一种假设，即西式饮食导致的肥胖改变了宿主肠道微生物种类，恶化了胃肠道和神经炎症症状的持久性。我们使用5个月的西方饮食喂养小鼠，这些小鼠在海湾战争（GW）前接受过化学暴露，以模拟部署的GW退伍军人的家庭期肥胖表型。西方饮食喂养的GWI小鼠的宿主微生物谱显示，产丁菌和免疫健康恢复菌显著减少。微生物组的改变与血清中il - 6水平升高、远端肠中Claudin-2、il - 6和il - 1β水平升高有关，同时伴有肝脏炎症病变和高胰岛素血症。微生物生态失调还与额叶皮层il - 6和il - 1β水平升高、小胶质细胞活化、脑源性神经营养因子（BDNF）水平降低以及磷酸化Tau蛋白（神经炎症导致认知缺陷风险增加的指标）积累升高有关。机制上，GWI小鼠的血清显著增加转化小胶质细胞的小胶质活化，增加酪氨酸自由基，分泌il - 6。总的来说，研究结果表明，GWI中存在的肥胖表型恶化了持续性胃肠道和神经元炎症，这可能导致恢复认知功能和缓解疲劳的不良结果，导致生活质量下降。
Persistence of Gulf War illness (GWI) pathology among deployed veterans is a clinical challenge even after almost three decades. Recent studies show a higher prevalence of obesity and metabolic disturbances among Gulf War veterans primarily due to the existence of post-traumatic stress disorder (PTSD), chronic fatigue, sedentary lifestyle, and consumption of a high-carbohydrate/high-fat diet. We test the hypothesis that obesity from a Western-style diet alters host gut microbial species and worsens gastrointestinal and neuroinflammatory symptom persistence. We used a 5 month Western diet feeding in mice that received prior Gulf War (GW) chemical exposure to mimic the home phase obese phenotype of the deployed GW veterans. The host microbial profile in the Western diet-fed GWI mice showed a significant decrease in butyrogenic and immune health-restoring bacteria. The altered microbiome was associated with increased levels of IL6 in the serum, Claudin-2, IL6, and IL1β in the distal intestine with concurrent inflammatory lesions in the liver and hyperinsulinemia. Microbial dysbiosis was also associated with frontal cortex levels of increased IL6 and IL1β, activated microglia, decreased levels of brain derived neurotrophic factor (BDNF), and higher accumulation of phosphorylated Tau, an indicator of neuroinflammation-led increased risk of cognitive deficiencies. Mechanistically, serum from Western diet-fed mice with GWI significantly increased microglial activation in transformed microglial cells, increased tyrosyl radicals, and secreted IL6. Collectively, the results suggest that an existing obese phenotype in GWI worsens persistent gastrointestinal and neuronal inflammation, which may contribute to poor outcomes in restoring cognitive function and resolving fatigue, leading to the deterioration of quality of life.
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影响因子：
3.8
作者：
Khaiboullina, Svetlana F.;DeMeirleir, Kenny L.;Lombardi, Vincent C.
通讯作者：
Lombardi, Vincent C.
影响因子：
5.7
作者：
Breland, Jessica Y.;Phibbs, Ciaran S.;Frayne, SusanM.
通讯作者：
Frayne, SusanM.
影响因子：
5
作者：
Kelsall, Helen L.;McKenzie, Dean P.;Dwyer, Terence
通讯作者：
Dwyer, Terence
DOI：
10.1073/pnas.1219451110
发表时间：
2013-05-28
影响因子：
11.1
作者：
Everard, Amandine;Belzer, Clara;Cani, Patrice D.
通讯作者：
Cani, Patrice D.
影响因子：
9.4
作者：
Bosshard, PP;Zbinden, R;Böttger, EC
通讯作者：
Böttger, EC