Manuela Berto Pucca
Julio Villena
Gislane Lelis Vilela de Oliveira- 1Department of Clinical Analysis, School of Pharmaceutical Sciences, São Paulo State University (UNESP), Araraquara, Brazil
- 2Laboratory of Immunobiotechnology, Reference Centre for Lactobacilli (CERELA-National Council of Scientific and Technological Research), San Miguel de Tucumán, Argentina
- 3Food and Feed Immunology Group, Laboratory of Animal Products Chemistry, Graduate School of Agricultural Science, Tohoku University, Sendai, Japan
- 4Microbiology Program, Department of Food Science and Technology, Institute of Biosciences, Humanities and Exact Sciences (IBILCE), São Paulo State University (UNESP), São José do Rio Preto, Brazil
- 5Laboratory of Immunomodulation and Microbiota, Department of Chemical and Biological Sciences, Institute of Biosciences (IBB), São Paulo State University (UNESP), Botucatu, Brazil
Editorial on the Research Topic
Dietary habits, microbiota and autoimmune diseases
Particular emphasis is given to the dietary habits as one of the modulators of the microbiota-immune system axis, pointing to the importance of studies in the interface of nutrition, microbiology and immunology (1, 2). Studies showed that macronutrients, micronutrients, and the different dietary profiles shape the intestinal microbiota diversity and their metabolities, impacting the human health or disease (3–7). It is already known that the microbiota establishment in early-life plays an essential role in the development and maturation of mucosal and systemic immune system (8–11). In addition, the complex interaction between available nutrients and the intestinal microbiota are able to impact our immune responses throughout life, maintaining homeostatic conditions (12–15). The breakdown of this balanced diet-microbiota-immune system crosstalk can influence disease triggering, including immune-mediated diseases, including autoimmune and allergic diseases (16–18).
The autoimmune diseases are multifactorial conditions, involving genetic and environmental factors, as well as, a dysfunctional immune response and intestinal dysbiosis (19–21). Besides that, the increased incidence of autoimmune diseases worldwide (3–9%) is not explained by genetic background or infections, suggesting a fundamental role of westernized dietary habits and dysbiosis in disease development in industrialized societies (22–26). The nutrition-mediated disruption of the microbiota-immune system axis can lead to short and long-term effects, such as dysbiosis, mucosal barrier deterioration, leaky gut, microbial translocation to lamina propria and bloodstream, and systemic inflammation, impacting all of the gut-organ axis and our entire physiology (20, 27–30). Westernized diet includes high consumption of saturated fats, sugar, additives, and decreased fibers' intake (31, 32). Mediterranean or plant-based diets include high consumption of fruits, vegetables, whole-grains, including fibers and high quality fats (33–36). Western and Mediterranean diets are representative models of detrimental or beneficial dietary patterns, respectively (31).
The future of the microbiota-based nutrition is to prevent diseases in genetic predisposal individuals, and predict clinical phenotypes and diseases in order to guide personalized therapies. Moreover, the personalized microbiota-based diets could be designed using the computational machine learning to design diets that will modulate the microbiota-immune system axis and improve clinical responses in autoimmune diseases (37–42).
In this Research Topic of Frontiers in Nutrition, we aimed to assemble a series of articles that highlight how the dietary habits impact the microbiota-immune system axis, and could influence immune-mediated diseases. We aimed to collect studies that report mechanisms and personalized dietary-based interventions to modulate the microbiota-immune system axis and immune-mediated diseases. A total of six articles were accepted and 28 researchers participated in this Research Topic.
First of all, in a perspective article, Larsen discussed the possible factors involved in rising incidence of autoimmune diseases and the “old friends hypothesis” that states that “the decreased exposure to microbes/infections early in life promote a defective immune system maturation” and could be involved in worldwide spread of immune-mediated diseases. Also, the modulation of the gut microbiota though dietary interventions in young age could represent a preventive, as well as a therapeutic strategy in autoimmune diseases.
Multiple sclerosis (MS) is an autoimmune, chronic, inflammatory neurodegenerative disease of the central nervous system that affects young adults, and twice women (43). It is estimated that 2.8 million subjects are currently diagnosed with the disease, and the worldwide prevalence increased 30% since 2013, and are partially attributed to environmental changes, including industrialization and westernization diets, alterations of the gut microbiota, and intestinal permeability (44). The intestinal dysbiosis, leaky gut and bacterial translocation have been associated with MS susceptibility and progression (45). Hoffman et al. revised studies showing dysbiosis in mice with experimental autoimmune encephalomyelitis (EAE), and in MS patients. Then, authors compiled works concerning the influence of dietary components on EAE and MS patients, including the beneficial effect of dietary fibers, their metabolites and polyunsaturated fatty acids on neuroinflammation, as well as, supplementation with A, D, and E vitamins. Besides that, the mini-review discussed some dietary interventions applied in EAE models and in clinical settings, including Mediterranean and isoflavone diets, plant-based/low-protein intake, ketogenic diet, and intermittent fasting. Finally, researchers concluded that microbiota-based therapies through dietary interventions could function as adjunctive strategy for MS treatment.
Similarly, Bronzini et al. discussed how food-microbiota axis could support intestinal dysbiosis, immunologic deregulation and neuroinflammation in MS, favoring disease onset and progression. In addition, researchers included preclinical reports evaluating the role played by high-fat, high-salt, high-sugar diets on gut microbiota of EAE mice, as well as, the influence of dietary fibers, tryptofan, isoflavones, and calorie restriction in the gut-immunity on EAE. In MS patients, studies involving the impact of Mediterranean, ketogenic, low-salt, and calorie restriction diets were also considered as dietary intervention. To finalize the review, the authors discussed the applications of prebiotics, probiotics, and post-biotics as adjuvant therapy to treat MS, considering their capacity to induce an anti-inflammatory milieu and to provide metabolites that cross-feeds beneficial microbes from the gut microbiota.
The inflammatory bowel diseases (IBD) include chronic inflammatory conditions of the gastrointestinal tract, including Crohn's disease and ulcerative colitis. The worldwide IBD prevalence increases and affects 1 in 200 young subjects in Western countries (46). Crohn's disease (CD) involves genetic and environmental factors in the disease development, including deregulated immune responses against the commensal gut microbiota, and is characterized by chronic and progressive inflammation of the gastrointestinal tract (47, 48). Ulcerative colitis (UC) is a chronic inflammatory bowel disease that affects the colon and the rectum (49). Deficiencies in micronutrients' absorption are normally observed in patients with IBD (50, 51). The review from Wu et al. summarized the role of vitamins and minerals' supplementation in IBD patients, as well as the importance of monitoring these patients and replacement therapy for these nutrients.
The last two original articles discussed important aspects of the preference for ethanol and its relationship with immune and the central nervous systems and the association between dietary factors and asthma. It was proposed that in the brain integrating region of reward system, the striatum, the interaction of the immune response and the expression of the Lrrk2 gene is involved in the addiction to ethanol (52). In the article of Moreira-Júnior et al., the preference for ethanol and its relationship with the interplay between the immune and the central nervous systems was investigated. By using wild-type C57BL/6 mice as well as Il6-/- and Nfat-/- animals, the authors tested whether high fat and sugar diet intake and free choice for ethanol altered the expression of Lrrk2 and immune genes. The work reported an increased compulsive-like behavior, an up-regulation of inflammatory genes (Il6, Il1β, iNOS Tlr4, and Nfat) as well as a down-regulation of the regulatory cytokine Il10, the Lrrk2 gene, and the dopamine receptor (Drd2) in the striatum. It was also observed that the absence of Il6 and Nfat in mice did not alter their ethanol preference. These findings suggest that interactions between Lrrk2 gene expression, the immune system and behavior influence the abusive consumption of ethanol. The better understanding of the factors associated with the neurobiology of ethanol addiction may help to develop new therapeutic targets for this disease. The study of Yang et al. investigated the association between dietary factors and asthma using Mendelian randomization and the IEU Open GWAS project as the source of exposure and outcome datasets, considering various dietary factors (e.g., alcohol intake, processed meat intake, fruit intake, etc.). The results indicated that alcohol intake frequency was associated with an increased risk of asthma, while fresh fruit intake and dried fruit intake were found to be protective factors against asthma. However, no significant causal relationship was observed between asthma and the other dietary factors studied. These findings contribute to our understanding of the impact of specific dietary components on asthma risk and emphasize the importance of considering dietary factors in respiratory health research.
Collectively, the articles in this Research Topic showed important aspects of the role played by dietary habits in the microbiota-immune system axis and in the immune-mediated disease pathogenesis. Furthermore, the researchers pointed out for the importance to consider the nutrition and microbiota modulation as important factors that can be used as a preventive and therapeutic tool in immune-mediated diseases.
Author contributions
MP, JV, and GO wrote the editorial. All authors approved the final version.
Conflict of interest
The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
Publisher's note
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References
1. Barrea L, Muscogiuri G, Frias-Toral E, Laudisio D, Pugliese G, Castellucci B, et al. Nutrition and immune system: from the Mediterranean diet to dietary supplementary through the microbiota. Crit Rev Food Sci Nutr. (2021) 61:3066–90. doi: 10.1080/10408398.2020.1792826
2. Macpherson AJ, de Agüero MG, Ganal-Vonarburg SC. How nutrition and the maternal microbiota shape the neonatal immune system. Nat Rev Immunol. (2017) 17:508–17. doi: 10.1038/nri.2017.58
3. Beam A, Clinger E, Hao L. Effect of diet and dietary components on the composition of the gut microbiota. Nutrients. (2021) 13:2795. doi: 10.3390/nu13082795
4. Rinninella E, Tohumcu E, Raoul P, Fiorani M, Cintoni M, Mele MC, et al. The role of diet in shaping human gut microbiota. Best Pract Res Clin Gastroenterol. (2023) 62–3:101828. doi: 10.1016/j.bpg.2023.101828
5. Rinninella E, Cintoni M, Raoul P, Lopetuso LR, Scaldaferri F, Pulcini G, et al. Food components and dietary habits: keys for a healthy gut microbiota composition. Nutrients. (2019) 11:2393. doi: 10.3390/nu11102393
6. Zhang Y, Zhou M, Zhou Y, Guan X. Dietary components regulate chronic diseases through gut microbiota: a review. J Sci Food Agric. (2023) 2023:12732. doi: 10.1002/jsfa.12732
7. Gill SK, Rossi M, Bajka B, Whelan K. Dietary fibre in gastrointestinal health and disease. Nat Rev Gastroenterol Hepatol. (2021) 18:101–16. doi: 10.1038/s41575-020-00375-4
8. Milani C, Duranti S, Bottacini F, Casey E, Turroni F, Mahony J, et al. The first microbial colonizers of the human gut: composition, activities, and health implications of the infant gut microbiota. Microbiol Mol Biol Rev. (2017) 81:e00036–17. doi: 10.1128/MMBR.00036-17
9. Kapourchali FR, Cresci GAM. Early-life gut microbiome-the importance of maternal and infant factors in its establishment. Nutr Clin Pract Off Publ Am Soc Parenter Enter Nutr. (2020) 35:386–405. doi: 10.1002/ncp.10490
10. Kalbermatter C, Fernandez Trigo N, Christensen S, Ganal-Vonarburg SC. Maternal microbiota, early life colonization and breast milk drive immune development in the newborn. Front Immunol. (2021) 12:683022. doi: 10.3389/fimmu.2021.683022
11. Torow N, Hand TW, Hornef MW. Programmed and environmental determinants driving neonatal mucosal immune development. Immunity. (2023) 56:485–99. doi: 10.1016/j.immuni.2023.02.013
12. Belkaid Y, Harrison OJ. Homeostatic immunity and the microbiota. Immunity. (2017) 46:562–76. doi: 10.1016/j.immuni.2017.04.008
13. Belkaid Y, Hand TW. Role of the microbiota in immunity and inflammation. Cell. (2014) 157:121–41. doi: 10.1016/j.cell.2014.03.011
14. Rooks MG, Garrett WS. Gut microbiota, metabolites and host immunity. Nat Rev Immunol. (2016) 16:341–52. doi: 10.1038/nri.2016.42
15. Kayama H, Okumura R, Takeda K. Interaction between the microbiota, epithelia, and immune cells in the intestine. Annu Rev Immunol. (2020) 38:23–48. doi: 10.1146/annurev-immunol-070119-115104
16. Donald K, Finlay BB. Early-life interactions between the microbiota and immune system: impact on immune system development and atopic disease. Nat Rev Immunol. (2023) 23:874. doi: 10.1038/s41577-023-00874-w
17. Wolter M, Grant ET, Boudaud M, Steimle A, Pereira GV, Martens EC, et al. Leveraging diet to engineer the gut microbiome. Nat Rev Gastroenterol Hepatol. (2021) 18:885–902. doi: 10.1038/s41575-021-00512-7
18. Shim JA, Ryu JH, Jo Y, Hong C. The role of gut microbiota in T cell immunity and immune mediated disorders. Int J Biol Sci. (2023) 19:79430. doi: 10.7150/ijbs.79430
19. Miyauchi E, Shimokawa C, Steimle A, Desai MS, Ohno H. The impact of the gut microbiome on extra-intestinal autoimmune diseases. Nat Rev Immunol. (2022) 22:727. doi: 10.1038/s41577-022-00727-y
20. Christovich A, Luo XM. Gut microbiota, leaky gut, and autoimmune diseases. Front Immunol. (2022) 13:946248. doi: 10.3389/fimmu.2022.946248
21. Ruff WE, Greiling TM, Kriegel MA. Host-microbiota interactions in immune-mediated diseases. Nat Rev Microbiol. (2020) 18:521–38. doi: 10.1038/s41579-020-0367-2
22. Conrad N, Misra S, Verbakel JY, Verbeke G, Molenberghs G, Taylor PN, et al. Incidence, prevalence, and co-occurrence of autoimmune disorders over time and by age, sex, and socioeconomic status: a population-based cohort study of 22 million individuals in the UK. Lancet Lond Engl. (2023) 2023:S0140-673600457-9. doi: 10.1016/S0140-6736(23)00457-9
23. Miller FW. The increasing prevalence of autoimmunity and autoimmune diseases: an urgent call to action for improved understanding, diagnosis, treatment, and prevention. Curr Opin Immunol. (2023) 80:102266. doi: 10.1016/j.coi.2022.102266
24. Manzel A, Muller DN, Hafler DA, Erdman SE, Linker RA, Kleinewietfeld M. Role of “Western diet” in inflammatory autoimmune diseases. Curr Allergy Asthma Rep. (2014) 14:404. doi: 10.1007/s11882-013-0404-6
25. Thorburn AN, Macia L, Mackay CR. Diet, metabolites, and “western-lifestyle” inflammatory diseases. Immunity. (2014) 40:833–42. doi: 10.1016/j.immuni.2014.05.014
26. Hirschberg S, Gisevius B, Duscha A, Haghikia A. Implications of diet and the gut microbiome in neuroinflammatory and neurodegenerative diseases. Int J Mol Sci. (2019) 20:3109. doi: 10.3390/ijms20123109
27. Martinez JE, Kahana DD, Ghuman S, Wilson HP, Wilson J, Kim SCJ, et al. Unhealthy lifestyle and gut dysbiosis: a better understanding of the effects of poor diet and nicotine on the intestinal microbiome. Front Endocrinol. (2021) 12:667066. doi: 10.3389/fendo.2021.667066
28. Martel J, Chang SH, Ko YF, Hwang TL, Young JD, Ojcius DM. Gut barrier disruption and chronic disease. Trends Endocrinol Metab. (2022) 33:247–65. doi: 10.1016/j.tem.2022.01.002
29. Kinashi Y, Hase K. Partners in leaky gut syndrome: intestinal dysbiosis and autoimmunity. Front Immunol. (2021) 12:673708. doi: 10.3389/fimmu.2021.673708
30. Levy M, Kolodziejczyk AA, Thaiss CA, Elinav E. Dysbiosis and the immune system. Nat Rev Immunol. (2017) 17:219–32. doi: 10.1038/nri.2017.7
31. García-Montero C, Fraile-Martínez O, Gómez-Lahoz AM, Pekarek L, Castellanos AJ, Noguerales-Fraguas F, et al. Nutritional components in western diet versus Mediterranean diet at the gut microbiota-immune system interplay. Implicat Health Dis Nutr. (2021) 13:699. doi: 10.3390/nu13020699
32. Christ A, Lauterbach M, Latz E. Western diet and the immune system: an inflammatory connection. Immunity. (2019) 51:794–811. doi: 10.1016/j.immuni.2019.09.020
33. Cena H, Calder PC. Defining a healthy diet: evidence for the role of contemporary dietary patterns in health and disease. Nutrients. (2020) 12:334. doi: 10.3390/nu12020334
34. Martínez-González MA, Gea A, Ruiz-Canela M. The Mediterranean diet and cardiovascular health. Circ Res. (2019) 124:779–98. doi: 10.1161/CIRCRESAHA.118.313348
35. Dominguez LJ, Di Bella G, Veronese N, Barbagallo M. Impact of Mediterranean diet on chronic non-communicable diseases and longevity. Nutrients. (2021) 13:2028. doi: 10.3390/nu13062028
36. Sofi F, Cesari F, Abbate R, Gensini GF, Casini A. Adherence to Mediterranean diet and health status: meta-analysis. Br Med J. (2008) 337:a1344. doi: 10.1136/bmj.a1344
37. Wastyk HC, Fragiadakis GK, Perelman D, Dahan D, Merrill BD, Yu FB, et al. Gut-microbiota-targeted diets modulate human immune status. Cell. (2021) 184:4137–53.e14. doi: 10.1016/j.cell.2021.06.019
38. Gioia C, Lucchino B, Tarsitano MG, Iannuccelli C, Di Franco M. Dietary habits and nutrition in rheumatoid arthritis: can diet influence disease development and clinical manifestations? Nutrients. (2020) 12:1456. doi: 10.3390/nu12051456
39. Riccio P, Rossano R. Diet, gut microbiota, and vitamins D + A in multiple sclerosis. Neurother J Am Soc Exp Neurother. (2018) 15:75–91. doi: 10.1007/s13311-017-0581-4
40. Dourado E, Ferro M, Sousa Guerreiro C, Fonseca JE. Diet as a modulator of intestinal microbiota in rheumatoid arthritis. Nutrients. (2020) 12:3504. doi: 10.3390/nu12113504
41. Popov J, Caputi V, Nandeesha N, Rodriguez DA, Pai N. Microbiota-immune interactions in ulcerative colitis and colitis associated cancer and emerging microbiota-based therapies. Int J Mol Sci. (2021) 22:11365. doi: 10.3390/ijms222111365
42. Kolodziejczyk AA, Zheng D, Elinav E. Diet-microbiota interactions and personalized nutrition. Nat Rev Microbiol. (2019) 17:742–53. doi: 10.1038/s41579-019-0256-8
43. Charabati M, Wheeler MA, Weiner HL, Quintana FJ. Multiple sclerosis: neuroimmune crosstalk and therapeutic targeting. Cell. (2023) 186:1309–27. doi: 10.1016/j.cell.2023.03.008
44. Walton C, King R, Rechtman L, Kaye W, Leray E, Marrie RA, et al. Rising prevalence of multiple sclerosis worldwide: insights from the Atlas of MS, third edition. Mult Scler Houndmills Basingstoke Engl. (2020) 26:1816–21. doi: 10.1177/1352458520970841
45. Correale J, Hohlfeld R, Baranzini SE. The role of the gut microbiota in multiple sclerosis. Nat Rev Neurol. (2022) 18:544–58. doi: 10.1038/s41582-022-00697-8
46. Ng SC, Shi HY, Hamidi N, Underwood FE, Tang W, Benchimol EI, et al. Worldwide incidence and prevalence of inflammatory bowel disease in the 21st century: a systematic review of population-based studies. Lancet Lond Engl. (2017) 390:2769–78. doi: 10.1016/S0140-6736(17)32448-0
47. Roda G, Chien Ng S, Kotze PG, Argollo M, Panaccione R, Spinelli A, et al. Crohn's disease. Nat Rev Dis Primer. (2020) 6:22. doi: 10.1038/s41572-020-0193-x
48. Caruso R, Lo BC, Núñez G. Host-microbiota interactions in inflammatory bowel disease. Nat Rev Immunol. (2020) 20:411–26. doi: 10.1038/s41577-019-0268-7
49. Kobayashi T, Siegmund B, Le Berre C, Wei SC, Ferrante M, Shen B, et al. Ulcerative colitis. Nat Rev Dis Primer. (2020) 6:74. doi: 10.1038/s41572-020-0205-x
50. Yoon SM. Micronutrient deficiencies in inflammatory bowel disease: trivial or crucial? Intest Res. (2016) 14:109–10. doi: 10.5217/ir.2016.14.2.109
51. Hwang C, Ross V, Mahadevan U. Micronutrient deficiencies in inflammatory bowel disease: from A to zinc. Inflamm Bowel Dis. (2012) 18:1961–81. doi: 10.1002/ibd.22906
Keywords: nutrition, microbiota-immune system axis, gut microbiota, immune-mediated diseases, autoimmune diseases
Citation: Pucca MB, Villena J and de Oliveira GLV (2023) Editorial: Dietary habits, microbiota and autoimmune diseases. Front. Nutr. 10:1233863. doi: 10.3389/fnut.2023.1233863
Received: 02 June 2023; Accepted: 12 June 2023;
Published: 23 June 2023.
Edited and reviewed by: Willem Van Eden, Utrecht University, Netherlands
Copyright © 2023 Pucca, Villena and de Oliveira. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
*Correspondence: Gislane Lelis Vilela de Oliveira, Z2lzbGFuZS5sZWxpcyYjeDAwMDQwO3VuZXNwLmJy