Specific bacteria in your gut are involved in compulsive eating and obesity

 The research is presented today (Thursday) at the Federation of European Neuroscience Societies (FENS) Forum 2024 and is published simultaneously in the journal Gut.

Professor Elena Martín-García, from the Laboratory of Neuropharmacology-NeuroPhar in the Department of Medicine and Life Sciences at the Universitat Pompeu Fabra, Barcelona, Spain, told the FENS Forum: “A number of factors contribute to food addiction, which is characterised by loss of control over food intake and is associated with obesity, other eating disorders and alterations in the composition of bacteria in the gut – the gut microbiome. Until now, the mechanisms underlying this behavioural disorder were largely unknown.”

Biomarkers for food addiction

Speaking before the FENS Forum, Professor Rafael Maldonado, who leads the Laboratory, said: “These results from our study may allow us to identify new biomarkers for food addiction and, most importantly, to evaluate whether the beneficial bacteria could be used as potential new treatments for this obesity-related behaviour, which, at present, lacks any effective therapeutic approaches. Potential new treatments could involve using beneficial bacteria and dietary supplementation.”

Prof. Martín-García used the Yale Food Addiction Scale (YFAS 2.0) to diagnose food addiction in mice and humans. It contains 35 questions for humans to answer, and these can also be grouped into three criteria for use in mice: persistent food-seeking, high motivation to obtain food, and compulsive behaviour.

She and her colleagues investigated the gut bacteria in mice who were and were not addicted to food and found an increase in bacteria belonging to a group called the Proteobacteria phylum and a decrease in bacteria belonging to the Actinobacteria phylum in the food-addicted mice. These mice also had a decrease in the amount of another type of bacteria called Blautia from the Bacillota phylum.

The researchers used the YFAS to classify 88 patients into those who were addicted or not addicted to food. Similar to the findings in mice, decreases in Actinobacteria phylum and Blautia were seen in those who were food-addicted and increases in Proteobacteria phylum. Further analyses showed how the findings in humans correlated with those in mice.

Beneficial effects

Prof. Martín-García said: “The findings in both mice and humans suggested that specific microbiota could be protective in preventing food addiction. In particular, the strong similarities in the amount of Blautia underlined the potential beneficial effects of this particular gut bacteria. Therefore, we investigated the protective effects of oral administration of lactulose and rhamnose, which are non-digestible carbohydrates known as ‘prebiotics’ that can increase the amount of Blautia in the gut. We did this in mice and found that it led to an increase in the abundance of Blautia in mice faeces in parallel with dramatic improvements in food addiction. We saw similar improvements when we gave the mice a species of Blautia called Blautia wexlerae orally as a probiotic.

“The gut microbiota signatures in both mice and humans suggest possible non-beneficial effects of bacteria belonging to the Proteobacteria phylum and potential protective effects of increasing the abundance of Actinobacterial and Bacillota against the development of food addiction.”

Prof. Martín-García says the findings show how bacteria in the gut influence brain function and vice versa. “We have demonstrated for the first time a direct interaction between the gut composition and brain gene expression, revealing the complex and multifactorial origin of this important behavioural disorder related to obesity. Understanding the crosstalk between alterations in behaviour and bacteria in the gut constitutes a step forward for future treatments for food addiction and related eating disorders.”

She also described work investigating how microRNAs (miRNAs) – small, single-stranded molecules that regulate gene expression and contribute to almost any cellular process – are involved in food addiction. Changes in the expression of miRNAs may be involved in the mechanisms underlying the disorder.

Tough decoy

The researchers used a technique called Tough Decoy (TuD) to inhibit specific miRNAs in the medial prefrontal cortex (mPFC) of brains of mice in order to produce mice that were vulnerable to developing food addiction. The mPFC is the part of the brain involved in self-control and decision-making. It was these mice that were also used in the study described above – the food-addicted mice.

They found that inhibition of miRNA-29c-3p promoted persistence of response and enhanced the vulnerability of the mice to develop food addiction. Inhibiting another miRNA called miRNA-665-3p promoted compulsive behaviour and vulnerability to food addiction.

Prof. Maldonado said: “These two miRNAs could act as protective factors against food addiction. This helps us to understand the neurobiology of the loss of eating control, which plays a crucial role in obesity and related disorders. To understand these mechanisms further, we are now exploring how the gut microbiota and miRNA expression in the brain interact in mice.”

Professor Richard Roche, Deputy Head of the Department of Psychology at Maynooth University, Maynooth, County Kildare, Ireland, is chair of the FENS communication committee and was not involved in the research.

He said: “Compulsive eating and food addiction is a growing problem worldwide. There are many factors that contribute to it, in particular the environment that people live in and the availability of certain types of food. However, we’ve known for some time that there are probably contributing factors for eating disorders and the research by Professor Martín-García and colleagues shows how the different types of bacteria in the gut have an impact on brain function and vice versa in humans and mice. This understanding opens the way to developing potential new treatments for eating disorders, and we look forward to seeing more research in this area.”