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.
Dipro BosePunnag SahaAyan MondalBrian FanelliRatanesh K SethPatricia JanulewiczKimberly SullivanStephen LasleyRonnie HornerRita C ColwellAshok K ShettyNancy KlimasSaurabh ChatterjeePublished in: Nutrients (2020)
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.
Keyphrases
- weight loss
- high fat diet induced
- insulin resistance
- metabolic syndrome
- bariatric surgery
- physical activity
- high fat diet
- type diabetes
- adipose tissue
- oxidative stress
- south africa
- inflammatory response
- mouse model
- microbial community
- lipopolysaccharide induced
- public health
- mental health
- cardiovascular disease
- weight gain
- squamous cell carcinoma
- cell proliferation
- traumatic brain injury
- induced apoptosis
- functional connectivity
- lps induced
- minimally invasive
- risk factors
- spinal cord injury
- cell cycle arrest
- obese patients
- skeletal muscle
- sleep quality
- locally advanced
- brain injury
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