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Mental Health

Gut-Brain axis

Insights into the gut-brain pathways have revealed a complex communication system that not only ensures the proper maintenance of gastrointestinal homeostasis, but is likely to have multiple effects on affect, motivation, and higher brain functions. This communication system is called the “gut-brain axis” (GBA). Both neural and hormonal lines of communication combine to allow the brain to influence the activities of intestinal functional effector cells, such as immune cells, epithelial cells, enteric neurons, smooth muscle cells, interstitial cells of Cajal and enterochromaffin cells (Carabotti, 2015). These same cells, on the other hand, are under the influence of the gut microbiota, whose contributing role in brain-gut reciprocal communications has recently been assessed (Mayer, 2014). The enteric microbiota is distributed in the human gastrointestinal tract and, although each person’s microbiota profile is different, among healthy individuals the presence, relative abundance and distribution along the intestine of these bacterial phylotypes is similar.

The impact of microbiota on GBA has been further supported by studies finalized to the manipulation of gut microbiota through the use of probiotics and/or antibiotics. These studies also confirm that microbiota affects anxiety by influencing brain neurochemistry. Given the ability of gut microbiota to alter nutrient availability and the close relationship between nutrient sensing and peptide secretion by enteroendocrine cells, the interaction of microbiota and GBA might also occur through the release of biologically active peptides from enteroendocrine cells that can affect the GBA. (Carabotti, 2015) In turn, psychological distress leads to further dysfunction of the axis and increased intestinal permeability. (Moulton, 2019)

Researches on Mental Health and IBD

In recent years, as more focus is given to the importance of mental health, many researches regarding the connection between mental health and Inflammatory Bowel diseases (IBDs) have taken place(Abautret-Daly, 2018)( Mikocka-Walus, 2016). IBDs affect a variety of aspects in the daily life of a patient, both economical and personal. In most researches, a common pattern of questions was used for the evaluation of the mental state of the patients. The pattern consists of four main aspects that may cause worry; quality of life, unpredictability, symptoms and treatment.

Quality of life

In most cases, participants reported concerns about how IBD would affect their quality of life, which encompassed two main sub-themes; Normal life, Fear and Ιsolation. Normal life referred to how the condition interfered with their general life and consisted of general lifestyle, bowel movement frequency, career, social life, diet and travelling. As a lot of them concerned about the condition’s effect on their general lifestyle, mentioning “effects on life” and “inconvenience”.

Fear and isolation referred to fear about the consequences of having IBD. This consists of cancer, body image issues, family life, mortality and embarrassment. Participants concerned about getting cancer, due to the condition, specifying “Increased risk of cancer” and “That I will get bowel cancer and won’t be able to watch my kids grow up or do the things I want to do in life”. (Keeton, 2015) Isolation inevitably being a result of all of these actions.

Unpredictability

The unpredictable nature of IBD affects greatly how the patients view the diseases. The theme Unpredictability encompasses future and long-term health, surgery, flare, and control. Each one of these sub-themes referred to the unpredictable nature of the condition, as participants reported concern about their future and long term health, with statements such as “not knowing what lies ahead” and “will I ever be better than I am now?” “the thought of more surgery” and “more operations”. (Keeton, 2015)

Symptoms

Symptoms reported included pain, incontinence, low energy, diarrhea, bleeding and wind. Regarding pain, participants specified “pains” and “pains which tormented me”. Concerning incontinence, they mentioned losing control of bowel actions. (Keeton, 2015)

Treatment

Treatments consisted of medicine side effects, colostomy bag, cure and knowledge “side effects of medications” and “being on medication with adverse side effects”. (Keeton, 2015)

Gender related concerns

Studies have pointed out that health care providers need to include gender specific concerns into the treatment, as vulnerability may be conferred by female sex, early life stress and lifestyle behaviors, to ensure all patients’ needs are addressed (Keeton, 2015) (Moulton, 2019).

Depressive symptoms and Inflammation in IBD

Depressive symptoms are reported by more than 20% of people with inflammatory bowel disease (IBD), while sleep difficulties and fatigue are even more common. Co-morbid depressive symptoms predict a poor IBD course, including increased risk of relapse and surgery, which is inconsistently improved by psychological treatments (Moulton, 2019) (Abautret-Daly, 2018).

During the last two decades, a pathogenic role of inflammation has been advocated in mental illnesses, including depression, schizophrenia and bipolar disorders. Thus, an attractive model by which inflammation may link depressive symptoms and IBD was created. The evidence suggests that depressive symptoms, fatigue or sleep problems provide a biomarker for an aggressive form of IBD that is underpinned by a dysfunctional microbiome, which leads to over-active immune pathways (Moulton, 2019) (Abautret-Daly, 2018).

Treatment opportunities

This inflammation model presents several opportunities for intervention. First, several studies have suggested that the functioning of the HPA axis may be altered in patients with IBD and this may be important in relation to stress induced increases in disease activity. Chronically raised levels of inflammatory cytokines in the blood due to active IBD may thus blunt the response of the HPA axis to both inflammation and acute stress, as has been found in other chronic inflammatory diseases. The function of the ANS may also be altered in patients with IBD as some authors have reported marked autonomic nervous hyperreflexia in patients with UC and CD (Mawdsley, 2005). Psychological therapies can help to reduce levels of IBD distress, resulting in the reduction of IBDs’ effects on the HPA axis and inflammation. Antidepressant therapies can help to reduce inflammation and may restore HPA axis function. Systemic anti-inflammatory treatments, such as biological cytokine antagonists, can help to reduce the effects of inflammation on the brain. Finally, interventions to alter the gut microbiota and gut-specific anti-inflammatory treatments can reduce negative effects of the gut on driving the gut–brain axis and inflammation (Moulton, 2019).

The synthetic approach

How is synthetic biology going to help?

Synthetic biology can help provide innovative solutions to problems involving mental health issues. Providing an non - invasive way of monitoring gastrointestinal health, can benefit the patient fighting the physical and mental pain. Creating a platform that can provide real-time monitoring, tailored treatment based on information gathered from the inner world of each patient, gives the opportunity to live their lives without dietary restrictions. That will be accomplished by the terms of Synthetic biology, where Mechanics and Biology are combined to create a new pathway for people to understand their bodies and try to heal them. Amalthea aims to alleviate the symptoms by providing a personalized treatment, resulting in the normalization of the gut microbiota’s function. Thus, balancing the gut - brain axis and also, the psychology of the patient.

Future approach

As the human brain is 77of studies, more specific gut-brain researches must be executed to define a better picture of their connective nature in IBDs cases. More specifically, studies testing systemic and gut-specific agents in depression would help to define the most effective points at which inflammation can be modified to break the cycle of worsening depressive symptoms and IBD outcomes. Changes in depressive symptoms could be tracked over multiple time-points against changes in peripheral inflammation, gut inflammation and even central inflammation. Finally, comparison with other chronic inflammatory conditions would help to define whether there is a somatic subtype of depression that is driven by inflammation and seen across inflammatory conditions (Moulton, 2019).

References

Abautret-Daly, Á., Dempsey, E., Parra-Blanco, A., Medina, C., & Harkin, A. (2018). Gut-brain actions underlying comorbid anxiety and depression associated with inflammatory bowel disease. Acta neuropsychiatrica, 30(5), 275–296. https://doi.org/10.1017/neu.2017.3

Carabotti, M., Scirocco, A., Maselli, M. A., & Severi, C. (2015). The gut-brain axis: interactions between enteric microbiota, central and enteric nervous systems. Annals of gastroenterology, 28(2), 203–209.

Keeton RL, Mikocka-Walus A, Andrews JM. Concerns and worries in people living with inflammatory bowel disease (IBD): A mixed methods study. J Psychosom Res. 2015 Jun;78(6):573-8. doi: 10.1016/j.jpsychores.2014.12.004. Epub 2014 Dec 15. PMID: 25543858.

Mayer EA, Savidge T, Shulman RJ. Brain-gut microbiome interactions and functional bowel disorders. Gastroenterology. 2014 May;146(6):1500-12. doi: 10.1053/j.gastro.2014.02.037. Epub 2014 Feb 28. PMID: 24583088; PMCID: PMC4114504.

Mawdsley, J. E., & Rampton, D. S. (2005). Psychological stress in IBD: new insights into pathogenic and therapeutic implications. Gut, 54(10), 1481–1491. https://doi.org/10.1136/gut.2005.064261

Mikocka-Walus, A., Pittet, V., Rossel, J. B., von Känel, R., & Swiss IBD Cohort Study Group (2016). Symptoms of Depression and Anxiety Are Independently Associated With Clinical Recurrence of Inflammatory Bowel Disease. Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association, 14(6), 829–835.e1. https://doi.org/10.1016/j.cgh.2015.12.045

Moulton CD, Pavlidis P, Norton C, Norton S, Pariante C, Hayee B, Powell N. Depressive symptoms in inflammatory bowel disease: an extraintestinal manifestation of inflammation? Clin Exp Immunol. 2019 Sep;197(3):308-318. doi: 10.1111/cei.13276. Epub 2019 Mar 11. PMID: 30762873; PMCID: PMC6693970.