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Factors Influencing the Gut-Brain Axis

Frances Ralph

Author: Frances Ralph is a King's College London trained Registered Dietitian and health writer who works within the NHS and private practice. Her specialist areas include gastroenterology and nutrition support.

The gut-brain axis (GBA) is a bi-directional system of communication between the brain and the gastrointestinal tract. It links together the emotional and cognitive centres of the brain with peripheral control and function of the gut (1). Vast amounts of research into the GBA is being undertaken and thus, knowledge in this area is constantly evolving.

Factors influencing the gut-brain axis include:

Early Life Development

The enteric nervous system (ENS), also referred to as our ‘gut-brain’, begins to develop in utero (2). Laboratory-based studies on germ-free mice has shown that a lack of microbial colonisation negatively impacts nervous system development, neurotransmitter production, gastrointestinal function and stress response in animals (3). Emerging research in humans suggests that the early life microbiome is an important factor in later health outcomes and stress responses (4).

Stress and Trauma

Stress and trauma, especially during key early developmental stages can impact the development of neural communication pathways and the gut microbiome (4). In animal studies, chronic activation of the hypothalamic pituitary adrenal (HPA) axis due to stress leads to GBA pathway dysfunction (5). In animal models, external psychological stress changes the composition (4) and total mass of the gut microbiome (6). In humans, studies are limited, but prenatal stress has been found to significantly impact the offspring’s microflora, which has been related to reported changes in offspring gastrointestinal tract (GIT) function (7).

Pathogens and Immune Activation

Gut parasite infections can impact brain function; for example, mice infected with campylobacter jejuni exhibit anxiety-like behaviour (8). Gut microbial balance appears to act as an important intermediary and contributes to regulation of the host inflammatory response (4), which alters signaling in the GBA (9).


Studies using mouse models of brain injury show changes in the microbiome; this is thought to be mediated by altered GBA communication (3).


Dysbiosis may impact GBA communication by altering the production of microbe produced/mediated communication molecules. Conversely, dysregulation of the GBA can impact the physical environment of the gut microbiome, through changes in secretion of mucous and the biofilm layer where bacteria grow (6). Animal studies have shown that even short-term stress can significantly change microbiota composition and these changes can induce anxiety-like behaviour in mice (4).


In conclusion, the GBA is essential for bidirectional communication between the brain and the gut. There are many factors which appear to influence the GBA including early life development, stress, immune response, neurodegeneration and dysbiosis.

The majority of research on the GBA comes from animal studies and other preclinical models. Thus, caution is needed when interpreting the existing evidence base. Further high-quality, large scale human intervention studies are required across all clinical areas to advance our knowledge of the role of the GBA in health and disease.


  1. Jenkins T, Nguyen J, Polglaze K, Bertrand P. Influence of Tryptophan and Serotonin on Mood and Cognition with a Possible Role of the Gut-Brain Axis. Nutrients. 2016;8(1):56.
  2. Konturek S, Brzozowski T, Konturek P, Gonciarz M. Brain–Gut Axis and Neural Control. Reference Module in Biomedical Sciences. 2014;. 2015;28(2):203-209.
  3. Martin C, Osadchiy V, Kalani A, Mayer E. The Brain-Gut-Microbiome Axis. Cellular and Molecular Gastroenterology and Hepatology. 2018;6(2):133-148.
  4. Foster J, Rinaman L, Cryan J. Stress & the gut-brain axis: Regulation by the microbiome. Neurobiology of Stress. 2017;7:124-136.
  5. Long-Smith C, O’Riordan K, Clarke G, Stanton C, Dinan T, Cryan J. Microbiota-Gut-Brain Axis: New Therapeutic Opportunities. Annual Review of Pharmacology and Toxicology. 2020;60(1):477-502.
  6. Carabotti M, Scirocco A, Maselli M, Severi C. The gut-brain axis: interactions between enteric microbiota, central and enteric nervous systems. Ann Gastroenterol.
  7. Zijlmans M, Korpela K, Riksen-Walraven J, de Vos W, de Weerth C. Maternal prenatal stress is associated with the infant intestinal microbiota. Psychoneuroendocrinology. 2015;53:233-245.
  8. Lyte M, Varcoe J, Bailey M. Anxiogenic effect of subclinical bacterial infection in mice in the absence of overt immune activation. Physiology & Behavior. 1998;65(1):63-68.
  9. Mayer E. Gut feelings: the emerging biology of gut–brain communication. Nature Reviews Neuroscience. 2011;12(8):453-466.

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