Subtitle: It’s too naive to think anorexia arises from psychosocial factors alone, researchers argue.
Sitting at the 3rd most common disease affecting adolescent females, anorexia is characterized by severe calorie restriction — comorbid with anxiety and depression — that lead to the starvation and malfunctioning of many other organs. Anorexia is titled the most fatal mental illness.
Anorexia Etiology Revisited
“Psychological factors might be important but are unconvincing as the primary or major cause [of anorexia],” James Morris and colleague from Lancaster University, UK, wrote in Medical Hypothesis in 2016.
Anorexia is a functional or psychosomatic disease; psycho means mind and somatic means body. It’s a mind-body disease caused by a combination of psychological and physical factors.
Modern views of anorexia, however, neglect the physical cause of the disease, as Morris and team argued:
There might, for instance, be an increased incidence of physical and sexual abuse in childhood in those who go on to manifest functional disorders. It is easy to see how this could influence symptoms in adults but it stretches credulity to imagine abuse as the sole and sufficient cause of the functional disorder. Equally modern concepts of the perfect physical form promoted by the fashion industry will influence teenagers to diet but surely there must be something more profound and fundamental to induce emaciation and death by starvation or suicide.
Basically, Morris et al. question the idea of psychosocial factors being the sole cause of anorexia. It’s too simplistic and crédule, they thought.
It doesn’t explain why a subset of adolescents do not develop anorexia when they have been exposed to similar childhood and cultural experiences.
Many will quickly attribute this to differences in genetics, social support, or an individual’s innate resilience. While these may also contribute to the overall likelihood of developing anorexia, Morris et al. asked:
What if bacteria also play a role?
When Bacteria-Fighting Antibodies Attack the Brain
Morris et al. first observed that anorexia nervosa is 10x more prevalent in females than males, and so are autoimmune diseases.
They then cited several studies that found the presence of autoantibodies — that attack the serotonin neurons and appetite-regulating hormones/peptides— roaming in the blood and hypothalamus of anorexics. The levels of these autoantibodies also correlated with the severity of the eating disorder.
The hypothalamus is a brain region that controls human basic needs such as sleep, body temperature, thirst, and appetite. It’s also part of the limbic system — also called the reptilian brain — which is an ancient set of structures in the brain that governs instincts and emotions.
Where did these auto-antibodies come from? The studies that discovered them raised the possibility of bacterial infection(s). Upon encountering foreign entities, the immune system makes antibodies that bind to the bacteria surface — to neutralize or marked it for destruction by other immune cells.
If the bacterium shares a similar structure to some of the host’s proteins — a phenomenon called molecular mimicry — the antibodies will target both the bacteria and the host's own proteins.
The fact that these antibodies — now autoantibodies — are considered as allies makes things worse. The blood-brain barrier, for example, doesn’t see it as a threat — enabling these autoantibodies to easily enter the brain’s limbic system.
“Auto-antibodies acting on the [brain’s] limbic system could induce extremes of emotion including disgust and fear,” Morris et al. wrote.
“These then become linked, in the minds of adolescent girls, to culturally determined ideas of what is, and what is not, the ideal body shape and size.
It is then a small step for disgust and fear to be directed to food and obesity which the fashion industry currently demonises.”
Linking to Gut Dysbiosis
While Morris et al. have not pinpointed a specific bacterial agent, current scientific evidence suggests that it could be gut bacteria.
Sergueï Fetissov, MD and Professor of Physiology, and colleagues from Rouen University and Hospital in France published a pioneer finding in this regard — which Morris et al. cited in his Medical Hypothesis paper.
Fetissov and the team found that autoantibodies — attacking appetite-regulating peptides — in the bloodstream of anorexics have substantial sequence similarities to few known gut microbes and external pathogens.
Proteins having a similar string of amino acid sequences likely have similar structures. And similar structures indicate a higher chance of getting bound by the same antibody due to molecular mimicry.
“Numerous cases of sequence homology with these [appetite-regulating] peptides were identified among commensal and pathogenic micro-organisms including Lactobacilli, Bacteroides, Helicobacter pylori, Escherichia coli, and Candida species,” the authors wrote.
These are just some examples as they have also discovered 20 other such microbes that have similar protein sequences as the human appetite-regulating peptides. The team further showed that mice without a gut microbiome have lower levels of such autoantibodies than normal mice.
“Our data demonstrate multiple cases of molecular mimicry of regulatory peptides with microbial proteins, identifying micro-organisms as putative biological targets to be tested for their relevance to the normal or pathophysiologic mechanisms of appetite and emotion,” Fetissov et al. continued.
Linking to the Gut-Brain Axis
A 2019 review — written by Jochen Seitz, MD, and coordinator of eating disorders research at University Aachen and colleagues from Germany — took a more holistic approach to the bacterial implications of anorexia.
They look at the gut-brain axis and its associated immunology as a whole. They look at it as intricate biological machinery or systems that interact with one another (see figure below).
While providing evidence supporting that bacterial infection may confuse the immune system to make antibodies attacking the brain’s appetite-regulatory signals, they added more recent evidence on the gut microbiome profile of anorexics. Compared to non-anorexics, their gut showed a reduced microbial diversity and abnormal outgrowth of certain microbes.
“These digestive products of [microbial] protein fermentation [in anorexics] were previously found to increase PYY-production, a gastric peptide known to decrease appetite and increase depressive symptoms,” the German researchers wrote.
To Wrap It Up
A gut dysbiosis or dysregulated gut-brain axis leads to systemic inflammation, autoantibodies, and harmful microbial metabolites — all of which negatively affect the brain’s appetite signals.
This may trigger — or at least contribute to — the downward spiral leading to anorexia, in addition to genetic and psychosocial factors. To this end, Seitz et al. (2019) proposed for gut microbiome interventions in addition to traditional therapy for anorexia.
“The goals could be to increase the amount of energy harvested from the same quantity of food and to decrease gut permeability, inflammation and antibody formation, with the potential consequence of reducing depressive and anxious symptoms,” Seitz and colleagues emphasized.
“Beat welcomes any new research which might add to our knowledge of the causes of and triggers for eating disorders…Anorexia nervosa claims more lives than any other mental illness, and eating disorders cost the UK economy over £16 billion a year, so the need for more knowledge and better treatment is acute.”
This article was originally published in Microbial Instincts.