You are likely familiar with the serious consequences of anorexia for those who experience it, but you might not be aware that the disorder may not be purely psychological.
A recent review from researchers at the University of Oxford in the open-access journal Frontiers in Psychiatry examines the evidence that gut microbes could play a significant role in anorexia by affecting appetite, weight, and psychiatric issues such as anxiety and compulsive behavior, among others.
Intriguingly, the study also examines the potential for microbial treatments for anorexia, but highlights that we are just beginning to understand the complex relationship between gut microbes and disease.
“Anorexia nervosa is a very common psychiatric disorder and can be incredibly debilitating or even fatal, but is unfortunately still quite challenging to treat,” explained Ana Ghenciulescu, lead author of the review.
“Moreover, there has been a great deal of recent excitement about the idea that gut microbes affect many aspects of our health, including our mental health – and that this relationship goes both ways.”
Recent research has examined these questions in the context of anorexia, and Ghenciulescu and colleagues combed the literature to summarize these findings.
For instance, previous research has shown that anorexia patients may have more bacteria that digest the protective mucus layer of the gut, making the gut ‘leaky’ and contributing to chronic inflammation, which is associated with psychiatric symptoms.
However, it is difficult to tell whether the microbial imbalance in anorexia patients contributes to the disease, or whether it is simply an effect of their dramatically restricted diet.
This chicken and egg situation is a puzzle, but studies in mice may shed some light on the situation. While the experiments may seem a little strange, as they rely on the most readily available source of gut microbes, feces, the results are compelling.
“In a mouse study, researchers transferred fecal samples from anorexia patients to the guts of mice with no microbiome of their own,” said Ghenciulescu.
“Such mice gained less weight and developed more anxious and compulsive behaviors compared with mice who received feces from healthy patients. This suggests that their altered gut bacteria might be contributing to similar symptoms in anorexia patients as well.”
While these results are preliminary, they hint at the intriguing possibility that targeting the microbiome could be a viable treatment for anorexia. Promoting and maintaining a better microbial balance may help to reduce some of the symptoms of anorexia.
So, what might such treatments look like? It could as simple as taking probiotic supplements, or may involve fecal transplants. However, the review highlights that our understanding of the relationship between gut microbes and anorexia is very much in its infancy.
“There is still no consensus over what a ‘healthy’ microbiome profile looks like, and the optimal composition is probably different for each person,” said Burnet. “Much more work needs to be done to understand the rich and highly complex microbial ecosystem within our gut.”
According to the DSM-5, anorexia nervosa (AN) is classified as a combination of low body weight, distorted body image and fear of gaining weight [1,2]. AN leads to severe somatic and endocrine consequences, including amenorrhea, low leptin and triiodothyronine levels, and increased ghrelin and cortisol levels.
The etiology of AN is not well understood; approximately 60% of the variance is genetic or epigenetic in origin, and psychosocial and individual factors also play important roles [3]. Due to its recently identified genetic associations with low body mass index, low incidence of type 2 diabetes, obesity, low fasting insulin and high HDL cholesterol levels, AN is now regarded as being of metabo-psychiatric origin [4].
AN has an incidence rate of 100–200/100,000 person-years in adolescent females, similar to that of type 1 diabetes [1,2], and a lifetime prevalence of 1–4% in Europe; it is thus one of the most common chronic illnesses in this age group [3]. In Germany and the UK, the numbers of hospital admissions for AN, especially in childhood and adolescence, have substantially risen in recent years [5,6], and the relapse rates remain high due to its often chronic course, culminating in the highest mortality rate of all psychiatric disorders [7].
The emotional burden for patients and their families and the socioeconomic costs to society due to treatment, care and missed work hours for patients with ANare approximately in the same range as those for depression and schizophrenia patients [8,9].
Multimodal treatment includes weight rehabilitation and psychotherapy but is far from sufficient. The underlying pathophysiology and factors that contribute to the chronicity of AN remain understudied.
To date, there are only nine studies on the alterations in the microbiota in patients with AN [10,11,12,13,14,15,16,17] and only two case studies of human fecal transplantation [18,19]. These studies suggest that the gut microbiota is altered in patients with AN, while transplantation of patient stool into rodents suggests that these alterations likely play an important role at least in the maintenance of the disease [20] if not in its etiology (see Figure 1).
We thus attempt to present these early findings as well as possible general mechanisms in the interplay of gut microbiota and the host to formulate hypotheses. Some of these mechanisms could also explain specific symptoms of AN.
However, research on AN significantly lags behind research on the microbiota as they relate to intestinal disorders, obesity or psychiatric illnesses, such as depression, as this research has already delineated some of these mechanisms. With this article, we thus hope to inspire similar research in the field of eating disorders and AN.
Effects of gut microbial products on brain functions and behavior in the intestinal tract and on immunological processes in patients with AN. (Adapted from [30]).
The gut microbiota and its interaction with the host are currently drawing increased attention from researchers and clinicians with respect to multiple diseases, both somatic and psychiatric [21,22]. There are now over 2000 microbial species known to inhabit the human gut [23], and each individual has a “personal” combination of approximately 500 species with a total weight of over 1 kg [24].
The major influencing factor that affect this combination of species is nutrition, while genetics, current illnesses, medication, stress, exercise and past experiences (such as mode of birth, having been breastfed, past illnesses and lifetime use of antibiotics) also appear to contribute [21,22].
Host–microbe interactions are equally manifold; as human evolution took place in a world full of microbes, symbiotic partnerships provided evolutionary advantages to both the microbes and host [25]. Gut microbes perform many functions, e.g., in the digestive system, gut microbes break down food with enzymes not expressed by humans, allowing for a greater diversity of nutrients to be used and more derivatives to be extracted, including fatty acids or essential vitamins [22].
Thus, the gut microbiota can increase or decrease the amount of energy extracted from the same amount of food, which is important for weight regulation. However, host–microbe interactions also include continuous cross-talk with intestinal cells, which influences gut-wall permeability, inflammatory and immunological processes and the secretion of gastric and bacteria-derived hormones [26].
Increasingly, complex direct and indirect interactions between the microbiota, gut and brain, termed the “microbiota-gut–brain axis”, have become increasingly apparent, and microbiota causally influence complex behaviors, such as learning, stress, depression and anxiety [22,27], all of which also play important roles in AN [3].
The potential mechanisms involve direct vagal nerve signaling, migration of immune cells into the brain, and changes in the secretion of cytokines, antibodies, hormones and nutritional components [21,22]. AN can probably be regarded as a helpful model for studying and learning about host-microbiota interactions, since AN is characterized by different factors, such as altered nutrition, weight, hormonal levels, gastrointestinal function and behaviors and the possibility of modifying these factors within a relatively short amount of time during therapy.
Furthermore, re-alimentation is a key factor in AN therapy, but controlled studies on how to refeed, with which nutrients and at what rate, remain scarce [28]. Given the important role of nutrition in the gut microbiota, the specific effects of re-alimentation remain unknown; failing to take into account interactions with gut microbes might actually cause iatrogenic harm [29].
On the other hand, nutritional interventions and pre- or probiotics (food enabling the growth of beneficial bacteria or beneficial bacteria themselves) could positively influence the gut microbiota and are currently becoming interesting research targets to complement current AN treatment.
In this review, we first describe the most important general findings with regard to the mechanisms of host-microbiota interactions. Then, we describe the potential role of these interactions in the pathophysiology and clinical course of patients with AN.
reference link: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7693512/
Source: Frontiers
