Role of Intestinal Microbiota in Patients with Anorexia Nervosa

Abstract

Anorexia nervosa is a psychiatric disorder characterized by severe low body weight, impaired self-body image, and intense fear of gaining weight, however its etiopathogenesis is not fully known. Some studies show that nutritional rehabilitation and corresponding weight restoration are not effective enough in the management of intestinal dysbiosis in patients with anorexia nervosa, but results are inconclusive. This work aims to review the existing studies to provide information about the possible role of intestinal microbiota in the pathophysiology of anorexia nervosa, characteristics of intestinal dysbiosis in patients with anorexia nervosa, and possible treatment approaches in the management of intestinal microbiota.

Keywords

• Anorexia nervosa
• microbiota
• dysbiosis

Anoreksiya Nervosalı Hastalarda İntestinal Mikrobiyotanın Rolü

Öz

Özet Düşük vücut ağırlığı, bozulmuş beden algısı ve kilo alma korkusu ile karakterize psikiyatrik bir bozukluk olan anoreksiya nervozanın etiyopatogenezi tam olarak bilinmemektedir. Literatürde yer alan çalışmalar anoreksiya nervosalı hastalarda beslenme rehabilitasyonunun ve yeniden ağırlık kazanımının intestinal disbiyoz yönetiminde yeterince etkin olmadığını göstermektedir, ancak çalışmaların sonuçları karmaşıktır. Bu derlemede intestinal mikrobiyotanın anoreksiya nervosa patofizyolojisindeki olası rolü, anoreksiya nervosalı hastalarda intestinal disbiyoza ilişkin özellikler ve intestinal mikrobiyota yönetiminde olası tedavi yaklaşımları hakkında bilgi verilmesi amaçlanmıştır.

Anahtar Kelimeler

• Anoreksiya nervoza
• mikrobiyota
• disbiyoz

Kaynakça

1. Agrawal, M., Aroniadis, O. C., Brandt, L. J., Kelly, C., Freeman, S., Surawicz, C. ve diğerleri. (2016). The long-term efficacy and safety of fecal microbiota transplant for recurrent, severe, and complicated Clostridium difficile infection in 146 elderly individuals. Journal of Clinical Gastroenterology, 50(5), 403-407.
2. Aizawa, E., Tsuji, H., Asahara, T., Takahashi, T., Teraishi, T., Yoshida, S. ve diğerleri. (2016). Possible association of Bifidobacterium and Lactobacillus in the gut microbiota of patients with major depressive disorder. Journal of Affective Disorders, 202, 254-257.
3. Al Omran, Y., & Aziz, Q. (2014). The brain-gut axis in health and disease. Microbial Endocrinology: The Microbiota-Gut-Brain Axis in Health and Disease, 135-153.
4. Arcelus, J., Mitchell, A. J., Wales, J., & Nielsen, S. (2011). Mortality rates in patients with anorexia nervosa and other eating disorders: a meta-analysis of 36 studies. Archives of General Psychiatry, 68(7), 724-731.
5. Armougom, F., Henry, M., Vialettes, B., Raccah, D., & Raoult, D. (2009). Monitoring bacterial community of human gut microbiota reveals an increase in Lactobacillus in obese patients and Methanogens in anorexic patients. PLoS One, 4(9), e7125.
6. Association, A. P. (2013). Diagnostic and statistical manual of mental disorders (DSM-5®): American Psychiatric Pub.
7. Bailey, M. T., Dowd, S. E., Galley, J. D., Hufnagle, A. R., Allen, R. G., & Lyte, M. (2011). Exposure to a social stressor alters the structure of the intestinal microbiota: implications for stressor-induced immunomodulation. Brain, Behavior, and Immunity, 25(3), 397-407.
8. Bajer, L., Kverka, M., Kostovcik, M., Macinga, P., Dvorak, J., Stehlikova, Z. ve diğerleri. (2017). Distinct gut microbiota profiles in patients with primary sclerosing cholangitis and ulcerative colitis. World Journal of Gastroenterology, 23(25), 4548.

9. Bambury, A., Sandhu, K., Cryan, J. F., & Dinan, T. G. (2018). Finding the needle in the haystack: systematic identification of psychobiotics. British Journal of Pharmacology, 175(24), 4430-4438.
10. Barcik, W., Boutin, R. C. T., Sokolowska, M., & Finlay, B. B. (2020). The Role of Lung and Gut Microbiota in the Pathology of Asthma. Immunity, 52(2), 241-255.
11. Bercik, P., Denou, E., Collins, J., Jackson, W., Lu, J., Jury, J. ve diğerleri. (2011). The intestinal microbiota affect central levels of brain-derived neurotropic factor and behavior in mice. Gastroenterology, 141(2), 599-609. e593.
12. Borgo, F., Riva, A., Benetti, A., Casiraghi, M. C., Bertelli, S., Garbossa, S. ve diğerleri. (2017). Microbiota in anorexia nervosa: the triangle between bacterial species, metabolites and psychological tests. PLoS One, 12(6), e0179739.
13. Bravo, J. A., Forsythe, P., Chew, M. V., Escaravage, E., Savignac, H. M., Dinan, T. G. ve diğerleri. (2011). Ingestion of Lactobacillus strain regulates emotional behavior and central GABA receptor expression in a mouse via the vagus nerve. Proceedings of the National Academy of Sciences, 108(38), 16050-16055.
14. Breton, J., Legrand, R., Akkermann, K., Järv, A., Harro, J., Déchelotte, P., & Fetissov, S. O. (2016). Elevated plasma concentrations of bacterial ClpB protein in patients with eating disorders. International Journal of Eating Disorders, 49(8), 805-808.
15. Byrne, C., Chambers, E., Morrison, D., & Frost, G. (2015). The role of short chain fatty acids in appetite regulation and energy homeostasis. International Journal of Obesity, 39(9), 1331-1338.
16. Carabotti, M., Scirocco, A., Maselli, M. A., & Severi, C. (2015). The gut-brain axis: interactions between enteric microbiota, central and enteric nervous systems. Annals of Gastroenterology: quarterly publication of the Hellenic Society of Gastroenterology, 28(2), 203.
17. Carbone, E. A., D’Amato, P., Vicchio, G., De Fazio, P., & Segura-Garcia, C. (2020). A systematic review on the role of microbiota in the pathogenesis and treatment of eating disorders. European Psychiatry, 1-40.
18. Carr, J., Kleiman, S. C., Bulik, C. M., Bulik-Sullivan, E. C., & Carroll, I. M. (2016). Can attention to the intestinal microbiota improve understanding and treatment of anorexia nervosa? Expert review of Gastroenterology & Hepatology, 10(5), 565-569.
19. Cass, K., McGuire, C., Bjork, I., Sobotka, N., Walsh, K., & Mehler, P. S. (2020). Medical Complications of Anorexia Nervosa. Psychosomatics, 61(6), 625-631.
20. Castro-Nallar, E., Bendall, M. L., Pérez-Losada, M., Sabuncyan, S., Severance, E. G., Dickerson, F. B. ve diğerleri. (2015). Composition, taxonomy and functional diversity of the oropharynx microbiome in individuals with schizophrenia and controls. PeerJ, 3, e1140.
21. Clark, A., & Mach, N. (2016). Exercise-induced stress behavior, gut-microbiota-brain axis and diet: a systematic review for athletes. Journal of the International Society of Sports Nutrition, 13(1), 1-21.
22. Cryan, J. F., & Dinan, T. G. (2012). Mind-altering microorganisms: the impact of the gut microbiota on brain and behaviour. Nature Reviews Neuroscience, 13(10), 701-712.
23. Currò, D., Ianiro, G., Pecere, S., Bibbò, S., & Cammarota, G. (2017). Probiotics, fibre and herbal medicinal products for functional and inflammatory bowel disorders. British Journal of Pharmacology, 174(11), 1426-1449.
24. Dalton, B., Bartholdy, S., Robinson, L., Solmi, M., Ibrahim, M. A., Breen, G. ve diğerleri. (2018). A meta-analysis of cytokine concentrations in eating disorders. Journal of Psychiatric Research, 103, 252-264.
25. de Clercq, N. C., Frissen, M. N., Davids, M., Groen, A. K., & Nieuwdorp, M. (2019). Weight gain after fecal microbiota transplantation in a patient with recurrent underweight following clinical recovery from anorexia nervosa. Psychotherapy and Psychosomatics, 88(1), 58-60.
26. de Clercq, N. C., Groen, A. K., Romijn, J. A., & Nieuwdorp, M. (2016). Gut microbiota in obesity and undernutrition. Advances in Nutrition, 7(6), 1080-1089.
27. Di Lodovico, L., Mondot, S., Doré, J., Mack, I., Hanachi, M., & Gorwood, P. (2020). Anorexia nervosa and gut microbiota: A systematic review and quantitative synthesis of pooled microbiological data. Progress in Neuro-Psychopharmacology and Biological Psychiatry, 110114.
28. Didari, T., Mozaffari, S., Nikfar, S., & Abdollahi, M. (2015). Effectiveness of probiotics in irritable bowel syndrome: updated systematic review with meta-analysis. World Journal of Gastroenterology, 21(10), 3072.
29. Farzi, A., Fröhlich, E. E., & Holzer, P. (2018). Gut microbiota and the neuroendocrine system. Neurotherapeutics, 15(1), 5-22.
30. Fetissov, S. O. (2017). Role of the gut microbiota in host appetite control: bacterial growth to animal feeding behaviour. Nature Reviews Endocrinology, 13(1), 11.
31. Foster, J. A., Rinaman, L., & Cryan, J. F. (2017). Stress & the gut-brain axis: regulation by the microbiome. Neurobiology of Stress, 7, 124-136.
32. Galmiche, M., Déchelotte, P., Lambert, G., & Tavolacci, M. P. (2019). Prevalence of eating disorders over the 2000–2018 period: a systematic literature review. American Journal of Clinical Nutrition, 109(5), 1402-1413.
33. Gorwood, P., Blanchet-Collet, C., Chartrel, N., Duclos, J., Dechelotte, P., Hanachi, M. ve diğerleri. (2016). New insights in anorexia nervosa. Frontiers in Neuroscience, 10, 256.
34. Hanachi, M., Manichanh, C., Schoenenberger, A., Pascal, V., Levenez, F., Cournède, N. ve diğerleri. (2019). Altered host-gut microbes symbiosis in severely malnourished anorexia nervosa (AN) patients undergoing enteral nutrition: An explicative factor of functional intestinal disorders? Clinical Nutrition, 38(5), 2304-2310.
35. Herpertz-Dahlmann, B., van Elburg, A., Castro-Fornieles, J., & Schmidt, U. (2015). ESCAP Expert Paper: New developments in the diagnosis and treatment of adolescent anorexia nervosa—a European perspective. European Child & Adolescent Psychiatry, 24(10), 1153-1167.
36. Herpertz-Dahlmann, B., Seitz, J., & Baines, J. (2017). Food matters: how the microbiome and gut–brain interaction might impact the development and course of anorexia nervosa. European Child & Adolescent Psychiatry, 26(9), 1031-1041.
37. Huang, T.-T., Lai, J.-B., Du, Y.-L., Xu, Y., Ruan, L.-M., & Hu, S.-H. (2019). Current understanding of gut microbiota in mood disorders: an update of human studies. Frontiers in Genetics, 10, 98.
38. Igudesman, D., Sweeney, M., Carroll, I. M., Mayer-Davis, E. J., & Bulik, C. M. (2019). Gut-brain interactions: implications for a role of the gut microbiota in the treatment and prognosis of anorexia nervosa and comparison to type I diabetes. Gastroenterology Clinics, 48(3), 343-356.
39. Jésus, P., Ouelaa, W., François, M., Riachy, L., Guérin, C., Aziz, M. ve diğerleri. (2014). Alteration of intestinal barrier function during activity-based anorexia in mice. Clinical Nutrition, 33(6), 1046-1053.
40. Jiang, H., Ling, Z., Zhang, Y., Mao, H., Ma, Z., Yin, Y. ve diğerleri. (2015). Altered fecal microbiota composition in patients with major depressive disorder. Brain, Behavior, and Immunity, 48, 186-194.
41. Karakula-Juchnowicz, H., Pankowicz, H., Juchnowicz, D., Valverde Piedra, J., & Malecka-Massalska, T. (2017). Intestinal microbiota–a key to understanding the pathophysiology of anorexia nervosa. Psychiatria Polska, 51(5), 859-870.
42. Kaye, W. H., Wierenga, C. E., Bailer, U. F., Simmons, A. N., & Bischoff-Grethe, A. (2013). Nothing tastes as good as skinny feels: the neurobiology of anorexia nervosa. Trends in Neurosciences, 36(2), 110-120.
43. Kelly, J. R., Borre, Y., O'Brien, C., Patterson, E., El Aidy, S., Deane, J. ve diğerleri. (2016). Transferring the blues: depression-associated gut microbiota induces neurobehavioural changes in the rat. Journal of Psychiatric Research, 82, 109-118.
44. Keshavarzian, A., Green, S. J., Engen, P. A., Voigt, R. M., Naqib, A., Forsyth, C. B. ve diğerleri. (2015). Colonic bacterial composition in Parkinson's disease. Movement Disorders, 30(10), 1351-1360.
45. Kimura, I., Inoue, D., Maeda, T., Hara, T., Ichimura, A., Miyauchi, S. ve diğerleri. (2011). Short-chain fatty acids and ketones directly regulate sympathetic nervous system via G protein-coupled receptor 41 (GPR41). Proceedings of the National Academy of Sciences, 108(19), 8030-8035.
46. Kleiman, S. C., Watson, H. J., Bulik-Sullivan, E. C., Huh, E. Y., Tarantino, L. M., Bulik, C. M., & Carroll, I. M. (2015). The intestinal microbiota in acute anorexia nervosa and during renourishment: relationship to depression, anxiety, and eating disorder psychopathology. Psychosomatic Medicine, 77(9), 969.
47. Lam, Y. Y., Maguire, S., Palacios, T., & Caterson, I. D. (2017). Are the gut bacteria telling us to eat or not to eat? Reviewing the role of gut microbiota in the etiology, disease progression and treatment of eating disorders. Nutrients, 9(6), 602.
48. Lederberg, J., & McCray, A. T. (2001). Ome SweetOmics--A genealogical treasury of words. The Scientist, 15(7), 8-8.
49. Li, H., He, J., & Jia, W. (2016). The influence of gut microbiota on drug metabolism and toxicity. Expert Opinion on Drug Metabolism & Toxicology, 12(1), 31-40.
50. Liu, R. T., Walsh, R. F., & Sheehan, A. E. (2019). Prebiotics and probiotics for depression and anxiety: a systematic review and meta-analysis of controlled clinical trials. Neuroscience & Biobehavioral Reviews, 102, 13-23.
51. Lyte, M. (2013). Microbial endocrinology in the microbiome-gut-brain axis: how bacterial production and utilization of neurochemicals influence behavior. PLoS Pathogens, 9(11), e1003726.
52. Mack, I., Cuntz, U., Grämer, C., Niedermaier, S., Pohl, C., Schwiertz, A. ve diğerleri. (2016). Weight gain in anorexia nervosa does not ameliorate the faecal microbiota, branched chain fatty acid profiles and gastrointestinal complaints. Scientific Reports, 6(1), 1-16.
53. Mackos, A. R., Maltz, R., & Bailey, M. T. (2017). The role of the commensal microbiota in adaptive and maladaptive stressor-induced immunomodulation. Hormones and Behavior, 88, 70-78.
54. Million, á., Angelakis, E., Maraninchi, M., Henry, M., Giorgi, R., Valero, R. ve diğerleri. (2013). Correlation between body mass index and gut concentrations of Lactobacillus reuteri, Bifidobacterium animalis, Methanobrevibacter smithii and Escherichia coli. International Journal of Obesity, 37(11), 1460-1466.
55. Monteleone, P., Carratu, R., Carteni, M., Generoso, M., Lamberti, M., De Magistris, L. ve diğerleri. (2004). Intestinal permeability is decreased in anorexia nervosa. Molecular Psychiatry, 9(1), 76-80.
56. Morita, C., Tsuji, H., Hata, T., Gondo, M., Takakura, S., Kawai, K. ve diğerleri. (2015). Gut dysbiosis in patients with anorexia nervosa. PLoS One, 10(12), e0145274. Mörkl, S., Lackner, S., Meinitzer, A., Mangge, H., Lehofer, M., Halwachs, B. ve diğerleri. (2018). Gut microbiota, dietary intakes and intestinal permeability reflected by serum zonulin in women. European Journal of Nutrition, 57(8), 2985-2997.
57. Mörkl, S., Lackner, S., Müller, W., Gorkiewicz, G., Kashofer, K., Oberascher, A. ve diğerleri. (2017). Gut microbiota and body composition in anorexia nervosa inpatients in comparison to athletes, overweight, obese, and normal weight controls. International Journal of Eating Disorders, 50(12), 1421-1431.
58. Morrison, D. J., & Preston, T. (2016). Formation of short chain fatty acids by the gut microbiota and their impact on human metabolism. Gut Microbes, 7(3), 189-200.
59. Moskowitz, L., & Weiselberg, E. (2017). Anorexia nervosa/atypical anorexia nervosa. Current Problems in Pediatric and Adolescent Health Care, 47(4), 70-84.
60. Neufeld, K., Kang, N., Bienenstock, J., & Foster, J. A. (2011). Reduced anxiety‐like behavior and central neurochemical change in germ‐free mice. Neurogastroenterology & Motility, 23(3), 255-e119.
61. Neuman, H., Debelius, J. W., Knight, R., & Koren, O. (2015). Microbial endocrinology: the interplay between the microbiota and the endocrine system. FEMS Microbiology Reviews, 39(4), 509-521.
62. Ni, J., Wu, G. D., Albenberg, L., & Tomov, V. T. (2017). Gut microbiota and IBD: causation or correlation? Nature Reviews Gastroenterology & Hepatology, 14(10), 573.
63. Nobuyuki, S., Yoichi, C., Yuji, A., Junko, S., Naomi, O., Xiao-Nian, Y. ve diğerleri. (2004). Postnatal microbial colonization programs the hypothalamic-pituitary-adrenal system for stress response in mice. Journal of Physiology, 558(1), 263-275.
64. Prochazkova, P., Roubalova, R., Dvorak, J., Tlaskalova-Hogenova, H., Cermakova, M., Tomasova, P. ve diğerleri. (2019). Microbiota, microbial metabolites, and barrier function in a patient with anorexia nervosa after fecal microbiota transplantation. Microorganisms, 7(9), 338.
65. Pulikkan, J., Maji, A., Dhakan, D. B., Saxena, R., Mohan, B., Anto, M. M. ve diğerleri. (2018). Gut microbial dysbiosis in Indian children with autism spectrum disorders. Microbial Ecology, 76(4), 1102-1114.
66. Rajilić–Stojanović, M., Biagi, E., Heilig, H. G., Kajander, K., Kekkonen, R. A., Tims, S., & de Vos, W. M. (2011). Global and deep molecular analysis of microbiota signatures in fecal samples from patients with irritable bowel syndrome. Gastroenterology, 141(5), 1792-1801.
67. Riva, G. (2016). Neurobiology of anorexia nervosa: serotonin dysfunctions link self-starvation with body image disturbances through an impaired body memory. Frontiers in Human Neuroscience, 10, 600.
68. Rosenbaum, M., Knight, R., & Leibel, R. L. (2015). The gut microbiota in human energy homeostasis and obesity. Trends in Endocrinology & Metabolism, 26(9), 493-501.
69. Roshchina, V. V. (2010). Evolutionary Considerations of Neurotransmitters in Microbial, Plant, and Animal Cells. In M. Lyte & P. P. E. Freestone (Eds.), Microbial Endocrinology: Interkingdom Signaling in Infectious Disease and Health (pp. 17-52). New York, NY: Springer New York.
70. Rowland, I., Gibson, G., Heinken, A., Scott, K., Swann, J., Thiele, I., & Tuohy, K. (2018). Gut microbiota functions: metabolism of nutrients and other food components. European Journal of Nutrition, 57(1), 1-24.
71. Ruusunen, A., Rocks, T., Jacka, F., & Loughman, A. (2019). The gut microbiome in anorexia nervosa: relevance for nutritional rehabilitation. Psychopharmacology, 1-14.
72. Sartor, R. B. (2008). Microbial influences in inflammatory bowel diseases. Gastroenterology, 134(2), 577-594.
73. Sato, Y., & Fukudo, S. (2015). Gastrointestinal symptoms and disorders in patients with eating disorders. Clinical Journal of Gastroenterology, 8(5), 255-263. Schwarz, E., Maukonen, J., Hyytiäinen, T., Kieseppä, T., Orešič, M., Sabunciyan, S. ve diğerleri. (2018). Analysis of microbiota in first episode psychosis identifies preliminary associations with symptom severity and treatment response. Schizophrenia Research, 192, 398-403.
74. Sekirov, I., Russell, S. L., Antunes, L. C. M., & Finlay, B. B. (2010). Gut Microbiota in Health and Disease. Physiol Rev, 90(3):859-904.
75. Simpson, C. A., Diaz-Arteche, C., Eliby, D., Schwartz, O. S., Simmons, J. G., & Cowan, C. S. (2020). The gut microbiota in anxiety and depression–A systematic review. Clinical Psychology Review, 101943.
76. Smith, P. A. (2015). The tantalizing links between gut microbes and the brain. Nature News, 526(7573), 312.
77. Solmi, M., Veronese, N., Favaro, A., Santonastaso, P., Manzato, E., Sergi, G., & Correll, C. U. (2015). Inflammatory cytokines and anorexia nervosa: A meta-analysis of cross-sectional and longitudinal studies. Psychoneuroendocrinology, 51, 237-252.
78. Soto-Martin, E. C., Warnke, I., Farquharson, F. M., Christodoulou, M., Horgan, G., Derrien, M. ve diğerleri. (2020). Vitamin biosynthesis by human gut butyrate-producing bacteria and cross-feeding in synthetic microbial communities. MBio, 11(4).
79. Strati, F., Cavalieri, D., Albanese, D., De Felice, C., Donati, C., Hayek, J. ve diğerleri. (2017). New evidences on the altered gut microbiota in autism spectrum disorders. Microbiome, 5(1), 1-11.
80. Tedelind, S., Westberg, F., Kjerrulf, M., & Vidal, A. (2007). Anti-inflammatory properties of the short-chain fatty acids acetate and propionate: a study with relevance to inflammatory bowel disease. World Journal of Gastroenterology, 13(20), 2826.
81. Tennoune, N., Chan, P., Breton, J., Legrand, R., Chabane, Y., Akkermann, K. ve diğerleri.(2014). Bacterial ClpB heat-shock protein, an antigen-mimetic of the anorexigenic peptide α-MSH, at the origin of eating disorders. Translational Psychiatry, 4(10), e458-e458.
82. Torres-Fuentes, C., Schellekens, H., Dinan, T. G., & Cryan, J. F. (2017). The microbiota–gut–brain axis in obesity. The Lancet Gastroenterology & Hepatology, 2(10), 747-756.
83. Van de Wouw, M., Schellekens, H., Dinan, T. G., & Cryan, J. F. (2017). Microbiota-gut-brain axis: modulator of host metabolism and appetite. Journal of Nutrition, 147(5), 727-745.
84. Vogt, N. M., Kerby, R. L., Dill-McFarland, K. A., Harding, S. J., Merluzzi, A. P., Johnson, S. C. ve diğerleri. (2017). Gut microbiome alterations in Alzheimer’s disease. Scientific Reports, 7(1), 1-11.
85. Walters, W. A., Xu, Z., & Knight, R. (2014). Meta-analyses of human gut microbes associated with obesity and IBD. FEBS Letters, 588(22), 4223-4233.
86. Wieërs, G., Belkhir, L., Enaud, R., Leclercq, S., Philippart de Foy, J.-M., Dequenne, I. ve diğerleri. (2020). How probiotics affect the microbiota. Frontiers in Cellular and Infection Microbiology, 9, 454.
87. Yamawaki, Y., Fuchikami, M., Morinobu, S., Segawa, M., Matsumoto, T., & Yamawaki, S. (2012). Antidepressant-like effect of sodium butyrate (HDAC inhibitor) and its molecular mechanism of action in the rat hippocampus. The World Journal of Biological Psychiatry, 13(6), 458-467.
88. Yoo, J. Y., Groer, M., Dutra, S. V. O., Sarkar, A., & McSkimming, D. I. (2020). Gut Microbiota and Immune System Interactions. Microorganisms, 8(10), 1587.
89. Zipfel, S., Giel, K. E., Bulik, C. M., Hay, P., & Schmidt, U. (2015). Anorexia nervosa: aetiology, assessment, and treatment. The Lancet Psychiatry, 2(12), 1099-1111.