The Gut‐Brain Connection: The Inflammatory Role of IL‐6 Caused by a Western Diet

Abstract

IntroductionAn increase in chronic proinflammatory immune activity is recognized as an increasingly fundamental element in relation to neurodegenerative disorders. Alzheimer’s disease (AD) is one of the most common neurodegenerative disorders, with recent evidence suggesting the Western Diet as a source for systemic inflammation. The communication fusing the gut to brain axis has been investigated through hepcidin, derived from both hepatocytes and dendritic cells. Hepcidin could potentially play an anti‐inflammatory role in the process of gut dysbiosis through a means of either a localized approach of nutritional immunity, or a systemic approach. Similarly, IL‐6 is a part of the gut‐brain axis. The levels of IL‐6 expression are affected by the gut microbiota and therefore sought to interplay a key role in cognitive function and decline, which could ultimately lead to several neurodegenerative diseases such as Alzheimer’s. The production of IL‐6 is increased by inflammation and associated with sepsis, endotoxemia and treatment with pro inflammatory cytokines. The release of this cytokine peripherally influences the CNS by a ting on the microglia to stimulate a state of neuroinflammation. During inflammation, proinflammatory cytokine IL‐6 is released from the intestinal mucosa and activates the Vagus nerve afferents. Hence, it could conceivably be hypothesized that IL‐6 activates gastrointestinal submucosal neurons through the brain‐gut axis. The aim of this study is to conduct a systematic review of literature through the search of available online medical databases containing information pertaining to gut dysbiosis and the primary communication between the brain‐gut axis.MethodsA total of 80 articles were retrieved from the databases of Pubmed, Google Scholar and Frontiers. Our method of assessment analyzed prominent keywords in our study pertaining to the small intestines, brain, liver, hepcidin, TMAO, BDNF, iron, astrocytes, WD, microbiota, gut microbiome, gut dysbiosis, iron, inflammation, oxidative stress, IL‐6, and vagus nerve. After reading the full‐text then extracting the findings from each study, our team organized those findings of brain, liver and gut biomolecules in relation to maintaining homeostasis and prevention of inflammation. The databases were assessed fall of 2021 following exportation of articles to a bibliographical database for further screening processes.ResultsThe results of this study indicate the optimal state of a healthy brain is IL‐6, hepcidin, ferritin and iron are at baseline levels. Whereas, in a dysbiosis state likely caused by WD, the brain responds by upregulating IL‐6, hepcidin and ferritin levels.ConclusionsIt would be interesting for a future study to experimentally focus on whether hepcidin upregulation induces the downregulation of iron in the neuron, or if the upregulation of iron in the neuron induces the downregulation of hepcidin in the setting of neuroinflammation.