Microbiome mind control over food appetite

Back in 2014, Joe Alcock, Athena Aktipis and Carlo Maley co-authored a paper in Bioessays, titled “Is eating behavior manipulated by the gastrointestinal microbiota? Evolutionary pressures and potential mechanisms.” In it they argued that gut microbes are under selective pressure to manipulate the eating behaviour of their host in order to increase their fitness – even if, sometimes, this comes at the expense of the host. Our microbiota can achieve this manipulation over our eating behaviour, they said, by generating cravings for foods that they specialize on or foods that suppress their competitors, or by inducing mental symptoms of depression and dissatisfaction in their hosts until we reward them – and ourselves – by consuming the food they hanker for. The authors put forward an obvious idea – although rather far-fetched given the present state of detailed knowledge of these effects – that appropriate manipulation of the microbiome could result in novel treatments to curb dietary excesses and control the obesity pandemic.

A recent paper in PLoS Biology provides empirical support for this idea through research on the eating behaviour of Drosophila. The paper, by Ribeiro et al, is titled “Commensal bacteria and essential amino acids control for choice behaviour and reproduction.” The interaction of microbiota with ingested nutrients, Ribeiro reminds us, has emerged as a major determinant of health and disease, including obesity. And commensal bacteria have also been proposed to affect a wide array of brain functions ranging from bulk food intake to anxiety, neurodevelopmental disorders, and social behavior. More recently, they say, the importance of commensal bacteria in controlling growth and in protecting children from malnutrition indicates that the microbiome could also play a pivotal role in protein homeostasis.

You are what you eat, the saying goes, and that pertains to humans and all animal species. Take protein intake, for example. As Ribeiro et al point out, although intake of dietary protein and amino-acids is vital you can have too much of a good thing – with detrimental effects on health. For this reason animals precisely control their intake of these vital nutrients – but how? In a series of experiments, Ribeiro et al manipulate the amino-acid diet of fruit flies and show that essential amino acids and gut bacteria are key modulators of protein appetite. They show that the lack of any one essential amino acid (eAA) from the diet produces a strong and specific appetite for proteinaceous or amino acid–rich food. The flies begin to binge on yeast. But flies with an appropriate microbiome do not develop this voracious protein appetite. Specifically, two gut bacterial species, Acetobacter pomorum and Lactobacillus, work together to suppress protein appetite. At the same time, bacteria in the gut release phagostimulants which, the authors say, likely aid replenishment of the gut with fresh bacteria. Flies continually replenish their microbiomes through feeding, Ribeiro explains. So, if commensal bacteria provide protection against eAA depletion, one might expect flies to prefer ingesting food containing commensals. This proved to be the case – flies ate more vigorously from a food source containing the commensal bacteria when compared to the same food without commensals and were therefore able to increase feeding behavior when bacteria were present in the food. This suggests that flies are able to actively modulate their feeding behavior to replenish or modify their microbiota in order to profit from the physiological benefits of the commensals. Furthermore, Ribeiro shows that if flies lack dietary essential amino acids it normally reduces their reproductive output – but that this effect is also rescued by these gut bacteria.

But how, exactly, does the microbiome buffer the flies against essential amino-acid shortfall and reduced reproductive efficiency? Ribeiro et al rule out, via experiment, two possibilities: That the bugs supply the flies directly with the missing amino-acids, or that the flies digest the bugs and release nutrients this way. What could be alternative mechanisms by which they influence behavior and egg production? Ribeiro suggests they could secrete metabolites that help the host to increase its ability to use its remaining AAs, thereby buffering the fly from the effects of dietary eAAs. Intriguingly, both yeast appetite and reproduction are thought to be regulated by the nutrient-sensitive TOR pathway, they say, and commensals have been shown to be able to modulate this. It is therefore possible that these bacteria act directly on nutrient sensing pathways by releasing metabolites that mimic the availability of eAAs, steering the flies into more efficient use of what resources they do have and away from binge-feeding.

This sort of research potently reminds us that no animal species is alone. It is a super-organism composed of its own genome and that of its microbiome acting in concert. As Ribiero concludes: “The metabolic repertoire of an organism is evolutionarily fixed in its genome. As such, it represents a static set which can mainly be modulated by transcriptional control. The observation that flies ingest more food containing commensal bacteria suggests that they might be able to direct their feeding behavior to replenish or maintain a specific microbiome composition. It is therefore attractive to speculate that the dynamic nature of the microbiome in flies paired with the ability to modulate the replenishment of gut microbes through feeding could allow them to extend and adapt their metabolic repertoire by exploiting that of the microbiome. This ability could partially explain the success of Drosophila in adapting to a wide range of habitats.”

There is a good popular account of this research in the latest edition of Scientific American, written by Knvul Sheikh. It is titled: “How gut bacteria tell their hosts what to eat: By suppressing or increasing cravings, microbes help the brain decide what foods the body ‘needs'”.