Anorexia: Yet Another Microbiome Induced Autoimmune Illness?

I’ve written a fair amount lately about the association of obesity to bacterial microbiome alterations, but have thus far, only had the chance to write a few times about the relationship of dysbiosis to anorexia nervosa (AN).  In my frenzy of reading these last couple of weeks, I came across an incredibly interesting article on the subject, which suggested something I had never read before:  many researchers now believe that, “…AN is an autoimmune disease caused by delayed exposure to common microorganisms (hygiene hypothesis) in which autoABS [auto antibodies] to appetite-regulating neuropeptides, neurotransmitters, and hypothalamic neurons, disturb appetite and result in decreased intake of food.”[i]  Is biome depletion once again rearing its ugly head?

In my first ever post about AN, I wrote about the relationship of other autoimmune diseases to the development of eating disorders:  “The researchers found ‘…significantly higher hazards of eating disorders for children and adolescents with autoimmune or autoinflammatory diseases:  36% higher hazard for anorexia nervosa, 73% for bulimia nervosa, and 72% for an eating disorder not otherwise specified.’”  I go on to mention that there is a growing body of literature associating eating disorders to alterations in the microbiome.  The second time I wrote about it, I went into these alterations in much more detail:  “Specifically, the authors of this paper note that there seems to be a general pattern found in those with anorexia:  ‘…a depletion of Lactobacillus and butyrate-producing Roseburia. In contrast, the relative abundance of Bifidobacteria, Proteobacteria, Akkermansia muciniphila and archaeon Methanobrevibacter smithii increases.’”

Now before you snap at me, “Judy, isn’t anorexia a cultural issue?  Isn’t it brought about by girls wanting to emulate the airbrushed, Photoshopped super models they see everywhere, in the media?” let’s take a big step back and remember that the human body is a whole – that the mind and body are one organism, and not separate entities.  Just as you get butterflies in your stomach when nervous or upset (the mind affects the body), remember too that it works both ways.  You get the flu, for example, and your body will engage in what is known as “sickness behavior” which is “…characterized by loss of appetite, reduction in activity and social interactions, depressed mood, and loss of libido.”  The communication between body and mind is bi-directional.  So the answer is YES – stress and anxiety brought about by attempting to emulate the fictional perfection of these models most certainly may play a part in the development of eating disorders:  “Genetic factors contribute to the etiology of AN based on various genetic studies.  Moreover, psychological risk factors as well as sociocultural influences and biological factors contribute to the risk of AN development.”

Remember:  stress and anxiety affect your microbiome, just as your microbiome affects your mind and behavior.  You have all read about this over and over on my blog.

So back now to AN and highlights from this article:

These authors restate what I have written about in the past regarding known microbiome alterations, including the archaea, Methanobrevibacter smithii.  And whoa…would you look at that!  I wrote about that too, in this post on archaea from earlier this month:  “An interesting couple of sentences from the abstract:  ‘They have been implicated in dysbiosis of the oral microbiota…They have also been associated with dysbiosis of the digestive tract microbiota linked to metabolic disorders (anorexia, malnutrition and obesity) and with lesions of the digestive tract (colon cancer).’”[iv]”

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These researchers state, “It was reported that AN patients possess greater concentrations of the archaeon Methanobrevibacter smithii in the gut.  This increase of a methane producing archaeon can result in the optimization of food transformation in a very low-calorie diet.”  That is, this particular archaea helps maximize the body’s ability to get energy from food, which is pretty critical when you’re barely eating.  They go on to say, “AN is associated intestinal microbial dysbiosis marked by lower microbial diversity and taxonomic differences in comparison with healthy controls.  This dysbiosis is also associated with depression and eating disorder psychopathology.”

Back to the autoimmune connection for a moment:  the intestinal bacterial play a crucial role in the “…increased permeability of tight junctions to macromolecules…This so called ‘leaky gut’ is associated with the development of inflammation, chronic diseases, sepsis, and also with some neurological and psychiatric disease.  The increased intestinal permeability enables the transport of microbial metabolites into the peripheral circulation….A ’leaky gut’ can be provoked by starvation…”

Bacterial metabolites, crossing through the leaky gut, look like invaders to the immune system, which then produces antibodies to them.  These cross-reacting autoABS have been observed and documented by researchers, who have found they react with chemicals in the body that stimulate appetite. In fact, in both humans and animals, antibodies to a hormone called alpha-melanocyte stimulating hormone (α-MSH), which, as the name suggests, stimulates appetite, are generated in response to a protein produced by some gut bacteria including E.coli.  In fact, “The levels of α-MSH autoABS correlate with core psychobehavioral abnormalities in patients with eating disorders.”

To sum that up:  metabolites from gut bacteria, like E.coli, cross the permeable gut barrier into the blood stream.  In response, the body produces antibodies to those metabolites, which also unfortunately, attack and destroy the α-MSH, which stimulates appetite.  And of course, the worse your appetite, the less you eat…and the leakier the gut becomes.  A vicious cycle is born.

Just a couple more items of interest:

As you may know, the bacteria of the gut produce many of our neurotransmitters.  It always surprises people when I tell them that 90% of the serotonin in their bodies is actually in the gut.  This article points this out, and goes on to state:  “The production of serotonin in the gut is affected by diet and regulates the motility of the gut as well as mood, appetite, sleep, and the cognitive functions of the individual.”  Dopamine, GABA, acetylcholine, etc., are also products of the gut flora.  Thus, anything that affects these microbes also affects the central nervous system.  Of course, decreased food intake also affects the immune system:  “Decreased food intake may have an impact on the interactions among the immune system and the CNS.  The impaired communication between these systems may be responsible for several associated psychiatric symptoms, such as stress, anxiety, and depression.”  So back to where I started this post:  psychological stress affects the microbiome…and the microbiome affects the emotional well-being and behavior of the person, including feeding behaviors.

The conclusion of the paper:  “Evidence has been published that behavioral disorders including eating disorders are accompanied by significant perturbations in the composition of the gut microbiota…The presence of antibodies primarily aimed against the compounds of the gut microbiota and cross reacting with neuroregulatory peptides in AN patients leads to a hypothesis that autoimmune mechanisms play an important role in the pathogenesis of AN.”

It will be incredibly interesting to see where this research leads.  I remember a few years ago, a doctor friend of mine went to a conference on complex inflammatory diseases.  The keynote speaker made a bold statement that really resonated with both my friend and me:  “Until proven otherwise, assume that all chronic illness is autoimmune.”  He may well turn out to be right!

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[i] Roubalova, R, et. al. Anorexia nervosa: gut microbiota-immune-brain interactions. Clinical Nutrition. 2019.  https://doi.org/10.1016/j.clnu.2019.03.023