Relationship between Human Gut Microbiota and Interleukin 6 Levels in Overweight and Obese Adults

Abstract

BackgroundGut microbial diversity and abundance can profoundly impact human health.Research has shown that obese individuals are likely to have altered microbiota compared to lean individuals. Obesity is often considered a pro‐inflammatory state, however the relationship between microbiota and inflammation is unclear. IL‐6 is a pro‐inflammatory cytokine that has been linked to disease states such as diabetes and obesity when chronically elevated. Establishing a relationship between IL‐6 and microbial abundance or diversity could improve diagnostic assessments or create new avenues for clinical treatment.MethodsTwenty‐two overweight or obese (BMI 29.1 kg/m2 ± 0.7) human subjects were recruited to participate in a digestibility study of a novel fiber. The study utilized a crossover design with a baseline period and three arms that lasted three weeks, each arm was separated from the next arm by a two week washout period. During the baseline and two washout periods subjects ate their usual diet. During the third week of each of the three arms, subjects consumed a low fiber controlled diet and either no, or a high or low dose of the novel fiber. Subjects collected fecal samples for the entire third week and participated in a test day where blood was repeatedly drawn. Bacterial genomic DNA was extracted from the pooled week of fecal samples. Microbial diversity and relative abundance of the different taxa present were determined based on sequencing the V4 region of bacterial 16S rRNA genes. Assays of blood drawn on the test days were utilized to determine IL‐6 concentration. R was used to assess the relationship between IL‐6 and microbial abundance.ResultsPrinciple Component Analysis as well as other statistical tests confirmed that no strong treatment effects were observed between the no, low, and high fiber arms with respect to the microbiota. IL‐6 data from each arm's test day were averaged across the day and ranged from 1.75pg/mL to 32.03pg/mL. Subjects with an IL‐6 concentration lower or greater than 20pg/mL were considered to be low and high, respectively. Least Partial Square Regression showed clear separation between the microbiota of subjects with higher as compared to lower concentrations of IL‐6. Further testing indicated that this separation was driven by significant (p = 0.04759) enrichment of Lactobacillus coryniformi, Lactobacillus helveticus, and Lactobacillus ruminis in the higher IL‐6 producers.ConclusionThis study demonstrates an increased abundance of Lactobacillus species in overweight and obese subjects with higher concentrations of circulating IL‐6. The relationship described between Lactobacillus and IL‐6 is surprising and requires further investigation. A limitation of this study is that it is not able to establish a causal factor so it remains unknown whether it is the IL‐6 level that shapes the microbial community or if it is the resident microbes that influence IL‐6 concentrations. Future research is needed to determine the exact nature of the relationship between IL‐6 and gut microbiota.Support or Funding InformationProject supported by funds from Ingredion Inc. and USDA, ARS CRIS Project 5306‐51530‐019‐00D