Individuals with Metabolic Syndrome Show Altered Fecal Lipidomic Profiles with No Signs of Intestinal Inflammation or Increased Intestinal Permeability

Abstract

Background: Metabolic Syndrome (MetS) is a clinical diagnosis where patients exhibit three out of the five risk factors: hypertriglyceridemia, low high-density lipoprotein (HDL) cholesterol, hyperglycemia, elevated blood pressure, or increased abdominal obesity. MetS arises due to dysregulated metabolic pathways that culminate with insulin resistance and put individuals at risk to develop various comorbidities with far-reaching medical consequences such as non-alcoholic fatty liver disease (NAFLD) and cardiovascular disease. As it stands, the exact pathogenesis of MetS as well as the involvement of the gastrointestinal tract in MetS is not fully understood. Our study aimed to evaluate intestinal health in human subjects with MetS. Methods: We examined MetS risk factors in individuals through body measurements and clinical and biochemical blood analysis. To evaluate intestinal health, gut inflammation was measured by fecal calprotectin, intestinal permeability through the lactulose-mannitol test, and utilized fecal metabolomics to examine alterations in the host–microbiota gut metabolism. Results: No signs of intestinal inflammation or increased intestinal permeability were observed in the MetS group compared to our control group. However, we found a significant increase in 417 lipid features of the gut lipidome in our MetS cohort. An identified fecal lipid, diacyl-glycerophosphocholine, showed a strong correlation with several MetS risk factors. Although our MetS cohort showed no signs of intestinal inflammation, they presented with increased levels of serum TNFα that also correlated with increasing triglyceride and fecal diacyl-glycerophosphocholine levels and decreasing HDL cholesterol levels. Conclusion: Taken together, our main results show that MetS subjects showed major alterations in fecal lipid profiles suggesting alterations in the intestinal host–microbiota metabolism that may arise before concrete signs of gut inflammation or intestinal permeability become apparent. Lastly, we posit that fecal metabolomics could serve as a non-invasive, accurate screening method for both MetS and NAFLD.

Chewing the fat: How lipidomics is changing our understanding of human health and disease in 2022

“…investigated the pathogenesis and involvement of the gastrointestinal tract with the syndrome through multiple experiments including an untargeted RPLC‐MS/MS analysis of faecal samples of people with MetS and healthy controls. No signs of intestinal inflammation or increased permeability were found in the MetS patients compared to the controls; however, significant increases in 417 lipid features, including various glycerolipids, glycerophospholipids, sphingolipids, fatty acyls, and polyketides, in the gut lipidome were observed, suggesting alterations of the intestinal host‐microbiota metabolism 277 . Further, Dalle et al.…”

“…Due to the elevated risk of mortality with these diseases, there is a need for strategies in its identification, prevention, and treatment within healthcare. In 2022, as evidenced in Figure 5, the bulk of research articles focussed on related diseases: CVD, 232–255 diabetes, 166,233,249,250,256–278 liver disease, 51,279–293 MetS 277,294,295 and obesity 277,295–305 …”

“…Bibliometric analyses of clinical lipidomics publications in 2022 according to separation techniques, detectors, and RPLC columns used …”

“…Bibliometric analyses of clinical lipidomics publications in 2022 using Scopus search terms “lipidomics” AND “clinic*” on 15 th December 2022 …”

“…,51,[279][280][281][282][283][284][285][286][287][288][289][290][291][292][293] MetS277,294,295 and obesity 277,[295][296][297][298][299][300][301][302][303][304][305]. Coleman et al investigated the pathogenesis and involvement of the gastrointestinal tract with the syndrome through multiple experiments including an untargeted RPLC-MS/MS analysis of faecal samples of people with MetS and healthy controls.…”