The gut-brain axis and obesity

Microbiota are able to modulate ghrelinergic signalling; there has been some translational evaluation of effects on obesity and the hypothalamic-pituitary-adrenal (HPA) axis with supplementation of the probiotic Bifidobacterium longum. However, more research is needed to assess whether Bifidobacterium longum can alter food reward signalling and food-motivated behaviour and whether microbiota are involved in aberrant food reward signalling in obesity [1].

The gut-brain axis plays a major role in regulating short- and long-term appetite, food reward, and the body’s metabolism, Dr Harriët Schellekens (University of Cork, Ireland) explained [1]. Ghrelin –the hunger hormone– is pivotal in the regulation of homeostatic energy balance, metabolism, and central regulation of appetite and reward mechanisms in haedonic eating behaviour [2]. Chronic and acute stress can increase ghrelin secretion and induces the consumption of caloric dense comfort food (i.e. junk food) (see Figure). This has been implicated as one of the major contributors to the increased prevalence of obesity.

Figure: The influence of ghrelin on obesity, anxiety, and depression [2]



Adapted from Schellekens et al. [2]

Furthermore, ghrelin is a critical factor at the interface of homeostatic control of appetite and reward circuitries, which modulates the haedonic aspects of food intake but also adds to feelings of anxiety and depression [3]. Therefore, the ghrelinergic system is seen as an effective target for the development of successful anti-obesity pharmacotherapies, Dr Schellekens stated. “These therapies should not be focused on appetite alone, but also on selectively modulating the rewarding properties of food. This could have an impact on the psychological well-being of the individual who experiences stress, anxiety, or depression.”

Microbiota-driven mechanisms of metabolism and central appetite regulation play a key role in obesity and diabetes mellitus, as gut bacteria alter how humans store fat, balance levels of glucose in the blood, and respond to hormones that either result in feelings of hunger or satiety. “These gut bacteria metabolise food particles; if a ‘wrong’ mix of microbiota is present, this can enhance the development of obesity or diabetes mellitus starting right from birth [5].”

It is not surprising that research has focused on altering harmful gut bacteria into ‘healthy’ microbiota. This may be achieved by supplementation with the probiotic Bifidobacterium longum APC1472. In rats, this led to a decrease in fat deposits, leptin plasma, corticosterone and neuropeptide expression, and an increase in glucose tolerance. Similar effects were observed in humans [4]. However, this is only the starting point for future research which hopefully elucidates the mechanisms and the potential for diet and nutrition in promoting overall health.

 

1. Schellekens H. Novel insights into gut-brain signalling in reward and obesity. S.22.01. ECNP Congress 2020.
2. Schellekens H, et al. Pharmacol Ther. 2012 Sep;135(3):316-26.
3. Schellekens H, et al. Vitam Horm. 2013;91:285-323.
4. Schellekens H, et al. submitted.
5. Torres-Fuentes C, et al. Lancet Gastroenterol Hepatol. 2017 Oct;2(10):747-756.

Posted on 2 November 2020