In a recent article published in the Journal of Nature Mental Health, researchers examined neural reactivity to unhealthy and healthy food cues and gut metabolites to elucidate potential mechanisms linking discrimination and obesity. 

Background

Genetics, diet, exercise, and psychological factors contribute to obesity and obesity-related morbidities, and the prevalence of obesity in all minority subgroups in the United States (US) is widespread. However, few studies have directly examined the role of discrimination in the etiology of obesity.

Brain and gut bidirectional talk involve the vagus nerve, neurotransmitters, immune-inflammatory mechanisms, microbial metabolites, and the hypothalamic–pituitary-adrenal axis.

However, the brain-gut-microbiome (BGM) system is the most important when studying the potential link between discrimination and subsequent stress responses with obesity.

In response to discrimination-related stress, it likely activates the brain’s reward and cognitive control networks, deactivating frontal executive modulation and potentiating brain activity in limbic regions, triggering people to eat energy-dense, unhealthy foods. 

Similarly, stress disrupts glutamate metabolism, altering gut metabolites via oxidative stress, glutamatergic excitotoxicity, and inflammation, all mechanisms responsible for neuronal damage.

Glutamate’s role in executive control and reward processing is also highly relevant to the processing of food cues.

About the study

In the present study, researchers recruited 107 individuals (87 women) from Los Angeles and collected data regarding their age, gender, race/ethnicity, body mass index (BMI), socioeconomic status (SES), and diet.

Further, they provided samples for fecal metabolomics, clinical and behavioral measures, and functional magnetic resonance imaging (fMRI).

The team used the Everyday Discrimination Scale (EDS) to rate chronic experiences of unfair treatment. Based on average EDS scores, they categorized participants into high and low discrimination exposure (EDS > 10 and EDS ≤ 10).

They used a two-way analysis of variance (ANOVA) to examine the interactions between high vs. low discrimination groups and American vs. non-American diets on BMI.

The researchers asked all the participants to complete the food-cue task in the fMRI scanner, where they formed neural responses to images of five types of foods: unhealthy savory, unhealthy sweet, healthy savory, healthy sweet, and nonfood (control).

They could see each picture for three seconds and give responses ranging from 0 to 10, indicating their intention to eat those food items.

Next, the researchers performed a whole-brain analysis 

to fetch clusters (in all five contrasts) that they combined to develop a discrimination-related food-cue region of interest (ROI) mask and do a structural equation model (SEM) analysis.

A subset of 62 participants provided fecal samples, which helped the researchers compare 12 metabolites from the glutamate pathway between the high vs. low discrimination groups using generalized linear modeling.

Further, they performed several linear regression analyses to evaluate discrimination-induced effects on brain signal change(s) in the food-cue ROI mask (composite).

In these statistical analyses, researchers adjusted for all covariates, including BMI, age, gender, race, diet, and SES. In addition, they corrected multiple analytical comparisons using the false discovery rate (FDR) method outlined in the Benjamini–Hochberg procedure.

Results

Unhealthy sugar-rich foods have a rewarding and analgesic nature, and frontal-striatal regions control feeding behavior in response to reward and hedonic aspects of food.

In this study, the authors noted that unhealthy food cues elicited greater activation in the aforementioned brain regions, e.g., the insular and orbitofrontal cortex.

Conversely, brain regions implicated in cravings and executive control, the frontal pole, middle frontal gyrus, and superior frontal gyrus, reacted to healthy food cues.

EDS score correlated positively with greater reactivity to unhealthy sweet and savory foods and healthy food. The high vs. low discrimination groups showed more willingness to eat unhealthy foods (P = 0.048 and 0.174).

Further, the authors noted that more discrimination caused the elicitation of more amounts of glutamate metabolites, N-acetylglutamate and N-acetylglutamine, implicated in studies evaluating obesity pathophysiology.

Studies have also shown the role of these metabolites in the glutamate pathways involving oxidative stress and inflammation. 

Conclusions

Overall, the results showed complex associations between discrimination and brain-gut alterations, especially when evaluating brain reactivity to unhealthy sweet food cues.

Brain-targeted treatments (e.g., brain stimulation) could dampen an overactive food-reward system or enhance frontal control. Thus, it could be used as a neuromodulatory tool to normalize altered brain circuits associated with discrimination exposure. 

Similarly, a probiotic supplement or Mediterranean diet with anti-inflammatory benefits could help treat disrupted glutamatergic pathways.