The Gut-Brain-Microbiota Axis and IBS Risk Factors

Communication Pathways 

There is no single body system or pathway responsible for digestion. In contrast, the Gut-Brain-Microbiota Axis is a complex network that facilitates communication between the brain and the gut. Its components include the neural pathways, such as the Enteric Nervous System (ENS) and the Autonomic Nervous System (ANS), the Hypothalamic Pituitary Adrenal (HPA) axis and the immune pathway. 

Within the Gut-Brain-Microbiota Axis, the neural pathway is comprised of the vagus and enteric nerve, neurotransmitters, neuroactive metabolites and bioactive peptides. The vagus nerve is the longest cranial nerve and serves as a physical connection between the brain and the gut. It regulates various functions, including digestion and heart and respiratory rates. The gut microbiota communicate with the vagus nerve, which in turn influences digestive mechanisms [1]. 

Neurotransmitters such as serotonin, gamma-aminobutyric acid (GABA), dopamine, melatonin, histamine, acetylcholine, and adrenaline/noradrenaline also coordinate neural communication between the gut and the brain [1]. Notably, while neurotransmitters do not cross the intestinal mucosal barrier under normal digestive conditions, they do during states of inflammation [1]. This points toward just one of many ways digestive processes are compromised when the digestive tract is inflamed. In addition, low levels of the neurotransmitter GABA are associated with depression, schizophrenia and other psychological disorders, further underlining the important link between digestive and cognitive functions [2].

The ENS is embedded in diverse tissues and regulates gut motility and secretions. The gut microbiota can impact digestive dysfunction following early childhood stress and throughout adulthood through interactions with the ENS [3]. The ANS, on the other hand, consists of the sympathetic and parasympathetic systems and helps maintain physiological homeostasis. The ANS is responsible for the body’s “rest and digest” mechanisms and is closely tied to the body’s response in both health and disease states [1].

The HPA axis is a neuroendocrine system that regulates mood and emotions through hormonal mechanisms. The HPA axis involves the communication between the hypothalamus, pituitary gland, and adrenal glands. Cortisol, the main stress hormone, is produced as a result of HPA axis activation. Constantly elevated cortisol due to continual stress leads to dysregulation of the HPA axis. Early life events, such as trauma and stress, can also sensitize the HPA axis, which contributes to over stimulation of these pathways and may subsequently alter gut microbiota composition and gut barrier function later in life [4]. 

Lastly, the immune pathway is also intricately involved in the Gut-Brain-Microbiota Axis and many digestive processes. This pathway includes B cells, epithelial cells, goblet cells, endocrine cells, and the mucus membrane, which also play significant roles in regulation. Abnormal gut microbiota can activate the innate immune system, leading to the release of cytokines and subsequent immune responses. This activation can also affect the intestinal barrier, contributing to visceral hypersensitivity and dysmotility, among much more [1].

Role of SCFAs in the Gut-Brain-Microbiota Axis

Short Chain Fatty Acids (SCFAs) are organic acids produced in the colon through the bacterial fermentation of dietary fibers and resistant starch. As their name suggests, they are less than 6 carbons long and include metabolites such as acetate, propionate and butyrate. 

SCFAs play a crucial role in digestion by enhancing gut barrier integrity and permeability, increasing concentration of tight junctions, strengthening the mucus layer, regulating gut motility, modulating the immune system, controlling systemic neuroinflammation, regulating appetite and much more [5]. SCFAs also play a role in reducing colonic carcinogenesis and lowering blood pressure and communicate through neuroendocrine mechanisms to regulate pain sensing and psychological states, such as anxiety, depression and stress [5].

DGBIs & their Risk Factors

Disorders of Gut Brain Interaction (DGBIs) are a group of disorders characterized by gastrointestinal (GI) symptoms related to motility disturbances, visceral hypersensitivity, altered mucosal and immune function, gut microbiota, and/or central nervous system processing. IBS and Functional Dyspepsia are among the most recognized and researched DGBIs, with approximately 40% of adults in the United States meeting the criteria for at least one condition [6].

The risk factors for IBS are wide-ranging and research is ongoing. Factors strongly associated with IBS include long-term or recurrent antibiotic use in children, somatic pain conditions, psychiatric conditions and fatigue. Psychological factors such as anxiety, depression, neuroticism, insomnia, and schizophrenia are also correlated with IBS risk [2,7]. Post-infectious IBS and antibiotic-induced dysbiosis also remain widely recognized and significant risk factors.

Additionally, genetics and environmental exposures (exposome) can influence the development of IBS. While genetic factors were once considered a major risk factor for IBS, newer findings reveal heritability is only 5.8%, highlighting the importance of environmental exposure and life events in IBS development. Early-life trauma, particularly in individuals with a family history of depression, anxiety, or IBS, increases the risk of developing IBS and stressors in adulthood can also influence onset and frequency of symptoms [2].

Summary and Further Resources 

As more research is published, the nuances of how lifestyle, stress, genetics and the microbiota are connected and influence digestive processes are increasingly understood. Brain-gut abnormalities underlying IBS include altered GI motility, visceral hypersensitivity, changes in the gut microbiome, and structural and functional brain alterations, but there is likely more to this picture. It’s promising to see increased research dedicated to the role of genetic risk factors and the role of gut microbiota in IBS and other DGBIs, though more is undoubtedly needed [8].