Diet, inflammation and obesity: a three-way street

From the Hullar Lab, Public Health Sciences and Vaccine and Infectious Disease Divisions

Gut microbiota (GM), the microorganisms occupying an individual’s gastrointestinal tract are constantly changing over one’s lifetime. Recent evidence suggests that one’s gut microbiota could play a role in obesity, since obesity is associated with low-level chronic inflammation (microinflammation) and recent work has suggested that gut microbiota could contribute to the wide spread microinflammation. An underlying driver of this inflammation could be LPS (lipopolysaccharide), a cell wall component of Gram-negative bacteria that triggers a pro-inflammatory response through NFκ-B activation. Increased LPS has been found to be associated with C-reactive protein (CRP), which is a biomarker for inflammation. In work published in the ISME Journal, authors from Fred Hutch studied the interplay between obesity, inflammation, LPS, and GM species composition.

LPS binding protein (LBP) and CRP measured in plasma and stool samples were collected for GM analysis in 110 premenopausal women. In addition, three-day food records were used to assess diet. Women were divided into three equal groups (tertiles) based on measured LBP levels. CRP levels were statistically different between the three groups and were highest in the high LBP group, which also had higher total fat and saturated fat intake as well as percent body fat. GM communities were analyzed at the phylum level by pyrosequencing of the 16S rRNA . GM beta diversity, but not alpha diversity, was statically significant between groups (by unweighted Unifrac).  Several phlya of bacteria were associates with low levels of LBP, including Christensenellaceaea and Ruminococcaceae, and Bacteroides were linked to high levels (see figure).  Bacteroides were also associated with high levels of CRP, while Phascolarctobacterium was found in low CRP groups.

Heatmap showing the presence of specific bacteria in each LBP group (tertile), with dark red representing the most prevalent and light red the least.

Taken together these data suggest a potential link between bacterial species and increased microinflammation that could contribute to obesity. When asked about the study, first author Dr. Citronberg said, “findings from the study highlight the role of bacteria in inflammation and obesity. We found the genera Bacteroides, Gram-negative bacteria associated with increased systemic inflammation, were increased in participants with high LBP. In contrast, members of Christensenellaceae, a family of bacteria that are associated with lean body mass in other studies, were more dominant in the participants with low levels of LBP. In future research, it will be interesting to explore the association between Bacteroides and/or Christensenellaceae levels and the metabolome.”

Funding was provided by the National Institutes of Health, Kellogg Corporate Citizens Fund and Fred Hutch.

Citronberg JS, Curtis KR, White E, Newcomb PA, Newton K, Atkinson C, Song X, Lampe JW, Hullar MA. 2018. Association of gut microbial communities with plasma lipopolysaccharide-binding protein (LBP) in premenopausal women. ISME J.