Most cited article - PubMed ID 30952533
Anorexia nervosa: Gut microbiota-immune-brain interactions
BACKGROUND: Dyslipidemia and distorted fatty acid (FA) metabolism are frequent biochemical abnormalities associated with anorexia nervosa (AN). Gut microbiota is supposed to play an important role in the etiopathogenesis of AN. Apart from the digestive function of bile acids (BAs), these compounds have multiple metabolic functions due to the activation of specific receptors. OBJECTIVE/AIMS: The aims of the study were to investigate biochemical measures, including plasma lipids (lipoproteins, respectively), fatty acid (FA) patterns, and the profile of plasma Bas, in AN patients and healthy controls (CON). METHODS: Plasma phospholipid FA and BAs profiles were analyzed in 39 women with a restrictive type of AN (AN-R; median age 17 years) and in 35 CON women (median age 20 years). RESULTS: Compared to CON, AN had an increased concentration of HDL-C, increased content of palmitic acid, and decreased proportion of linoleic acid. Moreover, AN had a drop in the level of the sum of PUFAn-6 and increased delta 9 desaturase activity for stearic acid. In AN, we found decreased levels of plasma tauroursodeoxycholic acid (TUDCA). In AN, concentrations of 22:5n-6, 16:0, 20:3n-6 and fat mass index were predic-tors of HDL-C levels (R2 = 0.43). CONCLUSIONS: Patients with AN-R had an increased concentration of HDL-C, decreased levels of total PUFA n-6, and increased activity of D9D for stearic acid. Furthermore, AN exerted decreased levels of TUDCA. Therefore, a decreased level of TUDCA could potentially serve as a marker of AN.
- Keywords
- anorexia nervosa, fatty acid pattern, lipids and lipoproteins, long-chain polyunsaturated fatty acids of n-6 family, multiple linear regression analysis, plasma bile acid composition,
- MeSH
- Adult MeSH
- Dyslipidemias * blood etiology complications MeSH
- Taurochenodeoxycholic Acid * blood MeSH
- Humans MeSH
- Fatty Acids * blood MeSH
- Anorexia Nervosa * blood complications MeSH
- Adolescent MeSH
- Young Adult MeSH
- Case-Control Studies MeSH
- Bile Acids and Salts blood MeSH
- Check Tag
- Adult MeSH
- Humans MeSH
- Adolescent MeSH
- Young Adult MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Names of Substances
- Taurochenodeoxycholic Acid * MeSH
- Fatty Acids * MeSH
- ursodoxicoltaurine MeSH Browser
- Bile Acids and Salts MeSH
Anorexia nervosa (AN) is a life-threatening psychiatric disorder with not well-described pathogenesis. Besides the genetic and sociological factors, autoimmunity is also considered to take part in AN pathogenesis. We evaluated general serological factors showing the physiological state of 59 patients with AN at hospital admission and their discharge. We detected the altered levels of some general biochemical and immunological parameters. We also detected decreased levels of appetite-regulating alpha-melanocyte stimulating hormone (α-MSH) in patients at hospital admission. Moreover, elevated anti-α-MSH IgM levels and decreased anti-α-MSH IgA levels were observed in patients with AN. Therefore, we analyzed the gut microbiota composition with special focus on α-MSH antigen-mimetic containing microbes from the Enterobacteriaceae family. We correlated gut bacterial composition with anti-α-MSH Ig levels and detected decreasing IgG levels with increasing alpha diversity. The upregulation of pro-inflammatory cytokines IL-6, IL-17, and TNF-α were detected in patients with AN both prior and after hospitalization. We also evaluated the treatment outcome and improvement was observed in the majority of patients with AN. We provide new data about various serum biochemical parameters and their changes during the patients' hospitalization, with emphasis on the immune system, and its possible participation in AN pathogenesis.
- Keywords
- Enterobacteriaceae, alpha-melanocyte stimulating hormone, anorexia nervosa, autoantibody, immune system, microbiota, realimentation,
- Publication type
- Journal Article MeSH
The equilibrium and reciprocal actions among appetite-stimulating (orexigenic) and appetite-suppressing (anorexigenic) signals synthesized in the gut, brain, microbiome and adipose tissue (AT), seems to play a pivotal role in the regulation of food intake and feeding behavior, anxiety, and depression. A dysregulation of mechanisms controlling the energy balance may result in eating disorders such as anorexia nervosa (AN) and bulimia nervosa (BN). AN is a psychiatric disease defined by chronic self-induced extreme dietary restriction leading to an extremely low body weight and adiposity. BN is defined as out-of-control binge eating, which is compensated by self-induced vomiting, fasting, or excessive exercise. Certain gut microbiota-related compounds, like bacterial chaperone protein Escherichia coli caseinolytic protease B (ClpB) and food-derived antigens were recently described to trigger the production of autoantibodies cross-reacting with appetite-regulating hormones and neurotransmitters. Gut microbiome may be a potential manipulator for AT and energy homeostasis. Thus, the regulation of appetite, emotion, mood, and nutritional status is also under the control of neuroimmunoendocrine mechanisms by secretion of autoantibodies directed against neuropeptides, neuroactive metabolites, and peptides. In AN and BN, altered cholinergic, dopaminergic, adrenergic, and serotonergic relays may lead to abnormal AT, gut, and brain hormone secretion. The present review summarizes updated knowledge regarding the gut dysbiosis, gut-barrier permeability, short-chain fatty acids (SCFA), fecal microbial transplantation (FMT), blood-brain barrier permeability, and autoantibodies within the ghrelin and melanocortin systems in eating disorders. We expect that the new knowledge may be used for the development of a novel preventive and therapeutic approach for treatment of AN and BN.
- Keywords
- alpha-MSH, anorexia nervosa and bulimia, autoantibody, caseinolytic peptidase B, fecal microbial transplantation, ghrelin, gut and blood-brain barrier permeability, microbiome,
- MeSH
- Autoantibodies * MeSH
- Ghrelin immunology MeSH
- Insulin immunology MeSH
- Leptin immunology MeSH
- Humans MeSH
- Melanocyte-Stimulating Hormones immunology MeSH
- Neuropeptide Y immunology MeSH
- Feeding and Eating Disorders immunology microbiology MeSH
- Gastrointestinal Microbiome immunology MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Review MeSH
- Names of Substances
- Autoantibodies * MeSH
- Ghrelin MeSH
- Insulin MeSH
- Leptin MeSH
- Melanocyte-Stimulating Hormones MeSH
- Neuropeptide Y MeSH
Brain-gut microbiota interactions are intensively studied in connection with various neurological and psychiatric diseases. While anorexia nervosa (AN) pathophysiology is not entirely clear, it is presumably linked to microbiome dysbiosis. We aimed to elucidate the gut microbiota contribution in AN disease pathophysiology. We analyzed the composition and diversity of the gut microbiome of patients with AN (bacteriome and mycobiome) from stool samples before and after renourishment, and compared them to healthy controls. Further, levels of assorted neurotransmitters and short-chain fatty acids (SCFA) were analyzed in stool samples by MS and NMR, respectively. Biochemical, anthropometric, and psychometric profiles were assessed. The bacterial alpha-diversity parameter analyses revealed only increased Chao 1 index in patients with AN before the realimentation, reflecting their interindividual variation. Subsequently, core microbiota depletion signs were observed in patients with AN. Overrepresented OTUs (operation taxonomic units) in patients with AN taxonomically belonged to Alistipes, Clostridiales, Christensenellaceae, and Ruminococcaceae. Underrepresented OTUs in patients with AN were Faecalibacterium, Agathobacter, Bacteroides, Blautia, and Lachnospira. Patients exhibited greater interindividual variation in the gut bacteriome, as well as in metagenome content compared to controls, suggesting altered bacteriome functions. Patients had decreased levels of serotonin, GABA, dopamine, butyrate, and acetate in their stool samples compared to controls. Mycobiome analysis did not reveal significant differences in alpha diversity and fungal profile composition between patients with AN and healthy controls, nor any correlation of the fungal composition with the bacterial profile. Our results show the changed profile of the gut microbiome and its metabolites in patients with severe AN. Although therapeutic partial renourishment led to increased body mass index and improved psychometric parameters, SCFA, and neurotransmitter profiles, as well as microbial community compositions, did not change substantially during the hospitalization period, which can be potentially caused by only partial weight recovery.
- Keywords
- BMI, EDE-Q, Microbiome, SCFA, bacteriome, dysbiosis, gut-brain-microbiota axis, mycobiome, neurotransmitter, renourishment,
- MeSH
- Archaea classification growth & development MeSH
- Bacteria classification growth & development metabolism MeSH
- Adult MeSH
- Feces microbiology MeSH
- Fungi classification growth & development metabolism MeSH
- Body Mass Index MeSH
- Fatty Acids, Volatile metabolism MeSH
- Humans MeSH
- Longitudinal Studies MeSH
- Anorexia Nervosa metabolism microbiology MeSH
- Metagenome MeSH
- Young Adult MeSH
- Mycobiome MeSH
- Neurotransmitter Agents metabolism MeSH
- Brain-Gut Axis MeSH
- Gastrointestinal Microbiome * MeSH
- Check Tag
- Adult MeSH
- Humans MeSH
- Young Adult MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Names of Substances
- Fatty Acids, Volatile MeSH
- Neurotransmitter Agents MeSH
The change in the gut microbiome and microbial metabolites in a patient suffering from severe and enduring anorexia nervosa (AN) and diagnosed with small intestinal bacterial overgrowth syndrome (SIBO) was investigated. Microbial gut dysbiosis is associated with both AN and SIBO, and therefore gut microbiome changes by serial fecal microbiota transplantation (FMT) is a possible therapeutic modality. This study assessed the effects of FMT on gut barrier function, microbiota composition, and the levels of bacterial metabolic products. The patient treatment with FMT led to the improvement of gut barrier function, which was altered prior to FMT. Very low bacterial alpha diversity, a lack of beneficial bacteria, together with a great abundance of fungal species were observed in the patient stool sample before FMT. After FMT, both bacterial species richness and gut microbiome evenness increased in the patient, while the fungal alpha diversity decreased. The total short-chain fatty acids (SCFAs) levels (molecules presenting an important source of energy for epithelial gut cells) gradually increased after FMT. Contrarily, one of the most abundant intestinal neurotransmitters, serotonin, tended to decrease throughout the observation period. Overall, gut microbial dysbiosis improvement after FMT was considered. However, there were no signs of patient clinical improvement. The need for an in-depth analysis of the donor´s stool and correct selection pre-FMT is evident.
