Gut microbiota in forty cases of egyptian relapsing remitting multiple sclerosis
-
Sherein G. Elgendy
,
Rawan Abd-Elhameed
,
Enas Daef
,
Shereen M. Mohammed
,
Hebatallah M. Hassan
,
Mohamed A. El-Mokhtar
,
Ahmed Nasreldein
,
Eman M. Khedr
Abstract
Background and Objectives: Gut microbiota is assumed to play an essential role in the pathogenesis of multiple sclerosis (MS). This study aimed to investigate the abundance of some gut microbiota among Egyptian patients with relapsing remitting multiple sclerosis (RR-MS).
Materials and Methods: Forty cases of RR-MS diagnosed according to McDonald diagnostic criteria (2017) were recruited consecutively from the Department of Neurology, Assiut University Hospitals. The results were compared with 22 healthy age and sex matched control subjects. DNA was extracted from stool and measures made of concentration and copy number of bacterial organisms by real-time PCR using group specific primers for 16S rRNA targeting predominant genera of gut microbiota previously hypothesized to participate in MS pathogenesis.
Results: The mean age was 31.4 ± 8.8 yrs; 75% of the patients were women. The mean and SD of EDSS score was 3.43 ± 1.35. Seven cases had cervical cord plaques (17%). There were significantly increased copy numbers of Desulfovibrio, Actinobacteria, Firmcutes, and Lactic acid bacteria in patients compared with the control group. In contrast there was a significantly lower level of Clostridium cluster IV in the patients. Patients who had EDSS < 3.5 had a significantly higher copy number of Actinobacteria, Bacteroidetes, and Bifidobacterium, compared with patients who had EDSS > 3.5. There was a significant negative correlation between duration of illness and copy number of Firmcutes, Akkermansia, and Lactic acid bacteria (P = 0.01, 0.04, and 0.004 respectively).
Conclusion: The changes in gut microbiota are associated with exacerbation of MS disease. Disruption of the intestinal microbiota results in the depletion or enrichment of certain bacteria that may affect the immune balance leading to predisposition to MS.
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2. Mirza A, Forbes JD, Zhu F, Bernstein CN, Van Domselaar G, Graham M, et al. The multiple sclerosis gut microbiota: a systematic review. Mult Scler Relat Disord 2020; 37: 101427.
3. Goodin DS. The epidemiology of multiple sclerosis: insights to a causal cascade. Handb Clin Neurol 2016; 138: 173-206.
4. Calvo-Barreiro L, Eixarch H, Montalban X, Espejo C. Combined therapies to treat complex diseases: the role of the gut microbiota in multiple sclerosis. Autoimmun Rev 2018; 17: 165-174.
5. Rothhammer V, Mascanfroni ID, Bunse L, Takenaka MC, Kenison JE, Mayo L, et al. Type I interferons and microbial metabolites of tryptophan modulate astrocyte activity and central nervous system inflammation via the aryl hydrocarbon receptor. Nat Med 2016; 22: 586-597.
6. Budhram A, Parvathy S, Kremenchutzky M, Silverman M. Breaking down the gut microbiome composition in multiple sclerosis. Mult Scler 2017; 23: 628-636.
7. Ma Q, Xing C, Long W, Wang HY, Liu Q, Wang RF. Impact of microbiota on central nervous system and neurological diseases: the gut-brain axis. J Neuroinflammation 2019; 16: 53.
8. Hill-Burns EM, Debelius JW, Morton JT, Wissemann WT, Lewis MR, Wallen ZD, et al. Parkinson's disease and parkinson's disease medications have distinct signatures of the gut microbiome. Mov Disord 2017; 32: 739-749.
9. Pulikkan J, Maji A, Dhakan DB, Saxena R, Mohan B, Anto MM, et al. Gut microbial dysbiosis in Indian children with autism spectrum disorders. Microb Ecol 2018; 76: 1102-1114.
10. Chen J, Chia N, Kalari KR, Yao JZ, Novotna M, Paz Soldan MM, et al. Multiple sclerosis patients have a distinct gut microbiota compared to healthy controls. Sci Rep 2016; 6: 28484.
11. Miyake S, Kim S, Suda W, Oshima K, Nakamura M, Matsuoka T, et al. Dysbiosis in the gut microbiota of patients with multiple sclerosis, with a striking depletion of species belonging to clostridia XIVa and IV clusters. PLoS One 2015; 10(9): e0137429.
12. Jangi S, Gandhi R, Cox LM, Li N, von Glehn F, Yan R, et al. Alterations of the human gut microbiome in multiple sclerosis. Nat Commun 2016; 7: 12015.
13. Haghikia A, Jörg S, Duscha A, Berg J, Manzel A, Waschbisch A, et al. Dietary fatty acids directly impact central nervous system autoimmunity via the small intestine. Immunity 2015; 43: 817-829.
14. Labbe A, Ganopolsky JG, Martoni CJ, Prakash S, Jones ML. Bacterial bile metabolising gene abundance in Crohn's, ulcerative colitis and type 2 diabetes metagenomes. PLoS One 2014; 9(12): e115175.
15. Thompson AJ, Banwell BL, Barkhof F, Carroll WM, Coetzee T, Comi G, et al. Diagnosis of multiple sclerosis: 2017 revisions of the McDonald criteria. Lancet Neurol 2018; 17: 162-173.
16. Leocani L, Rovaris M, Boneschi FM, Medaglini S, Rossi P, Martinelli V, et al. Multimodal evoked potentials to assess the evolution of multiple sclerosis: a longitudinal study. J Neurol Neurosurg Psychiatry 2006; 77: 1030-1035.
17. Pirker A, Stockenhuber A, Remely M, Harrant A, Hippe B, Kamhuber C, et al. Effects of antibiotic therapy on the gastrointestinal microbiota and the influence of Lactobacillus casei. Food Agric Immunol 2013; 24: 315-330.
18. Png CW, Linden SK, Gilshenan KS, Zoetendal EG, McSweeney CS, Sly LI, et al. Mucolytic bacteria with increased prevalence in IBD mucosa augment in vitro utilization of mucin by other bacteria. Am J Gastroenterol 2010; 105: 2420-2428.
19. Dridi B, Henry M, El Khechine A, Raoult D, Drancourt M. High prevalence of Methanobrevibacter smithii and Methanosphaera stadtmanae detected in the human gut using an improved DNA detection protocol. PLoS One 2009; 4(9): e7063.
20. Collado MC, Derrien M, Isolauri E, de Vos WM, Salminen S. Intestinal integrity and Akkermansia muciniphila, a mucin-degrading member of the intestinal microbiota present in infants, adults, and the elderly. Appl Environ Microbiol 2007; 73: 7767-7770.
21. Gałecka M, Szachta P, Bartnicka A, Łykowska-Szuber L, Eder P, Schwiertz A. Faecalibacterium prausnitzii and Crohn’s disease–is there any connection? Pol J Microbiol 2013; 62: 91-95.
22. Remely M, Dworzak S, Hippe B, Zwielehner J, Aumüller E, Brath H, et al. Abundance and diversity of microbiota in type 2 diabetes and obesity. J Diabetes Metab 2013; 4: 253.
23. Rose'Meyer RB, Mellick AS, Garnham BG, Harrison GJ, Massa HM, Griffiths LR. The measurement of adenosine and estrogen receptor expression in rat brains following ovariectomy using quantitative PCR analysis. Brain Res Brain Res Protoc 2003; 11: 9-18.
24. Rutledge RG, Côté C. Mathematics of quantitative kinetic PCR and the application of standard curves. Nucleic Acids Res 2003; 31: e93.
25. Ghaderian S, Shomali N, Behravesh S, Danbaran GR, Hemmatzadeh M, Aslani S, et al. The emerging role of lncRNAs in multiple sclerosis. J Neuroimmunol 2020; 347: 577347.
26. Waubant E, Lucas R, Mowry E, Graves J, Olsson T, Alfredsson L, et al. Environmental and genetic risk factors for MS: an integrated review. Ann Clin Transl Neurol 2019; 6: 1905-1922.
27. Goldenberg MM. Multiple sclerosis review. P T 2012; 37: 175-184.
28. Lavasani S, Dzhambazov B, Nouri M, Fak F, Buske S, Molin G, et al. A novel probiotic mixture exerts a therapeutic effect on experimental autoimmune encephalomyelitis mediated by IL-10 producing regulatory T cells. PLoS One 2010; 5(2): e9009.
29. Cantarel BL, Waubant E, Chehoud C, Kuczynski J, DeSantis TZ, Warrington J, et al. Gut microbiota in multiple sclerosis: possible influence of immunomodulators. J Investig Med 2015; 63: 729-734.
30. Cosorich I, Dalla-Costa G, Sorini C, Ferrarese R, Messina MJ, Dolpady J, et al. High frequency of intestinal TH17 cells correlates with microbiota alterations and disease activity in multiple sclerosis. Sci Adv 2017; 3(7): e1700492.
31. Wang Y, Yin Y, Chen X, Zhao Y, Wu Y, Li Y, et al. Induction of intestinal Th17 cells by flagellins from segmented filamentous bacteria. Front Immunol 2019; 10: 2750.
32. Tremlett H, Fadrosh DW, Faruqi AA, Hart J, Roalstad S, Graves J, et al. Gut microbiota composition and relapse risk in pediatric MS: a pilot study. J Neurol Sci 2016; 363: 153-157.
33. Korkina L, Kostyuk V, De Luca C, Pastore S. Plant phenylpropanoids as emerging anti-inflammatory agents. Mini Rev Med Chem 2011; 11: 823-835.
34. Schogor AL, Huws SA, Santos GT, Scollan ND, Hauck BD, Winters AL, et al. Ruminal Prevotella spp. may play an important role in the conversion of plant lignans into human health beneficial antioxidants. PLoS One 2014; 9(4): e87949.
35. Moussa L, Bezirard V, Salvador-Cartier C, Bacquie V, Lencina C, Leveque M, et al. A low dose of fermented soy germ alleviates gut barrier injury, hyperalgesia and faecal protease activity in a rat model of inflammatory bowel disease. PLoS One 2012; 7(11): e49547.
36. Leiva-Gea I, Sanchez-Alcoholado L, Martin-Tejedor B, Castellano-Castillo D, Moreno-Indias I, Urda-Cardona A, et al. Gut microbiota differs in composition and functionality between children with Type 1 diabetes and MODY2 and healthy control subjects: a case-control study. Diabetes Care 2018; 41: 2385-2395.
37. den Besten G, van Eunen K, Groen AK, Venema K, Reijngoud DJ, Bakker BM. The role of short-chain fatty acids in the interplay between diet, gut microbiota, and host energy metabolism. J Lipid Res 2013; 54: 2325-2340.
38. Wisniewski PJ, Dowden RA, Campbell SC. Role of dietary lipids in modulating inflammation through the gut microbiota. Nutrients 2019; 11: 117.
39. Gevers D, Kugathasan S, Denson LA, Vázquez-Baeza Y, Van Treuren W, Ren B, et al. The treatment-naive microbiome in new-onset Crohn’s disease. Cell Host Microbe 2014; 15: 382-392.
40. Chu F, Shi M, Lang Y, Shen D, Jin T, Zhu J, et al. Gut microbiota in multiple sclerosis and experimental autoimmune encephalomyelitis: current applications and future perspectives. Mediators Inflamm 2018; 2018: 8168717.
41. Jeraldo P, Hernandez A, Nielsen HB, Chen X, White BA, Goldenfeld N, et al. Capturing one of the human gut microbiome’s most wanted: reconstructing the genome of a novel butyrate-producing, clostridial scavenger from metagenomic sequence data. Front Microbiol 2016; 7: 783.
42. Tremlett H, Fadrosh DW, Faruqi AA, Zhu F, Hart J, Roalstad S, et al. Gut microbiota in early pediatric multiple sclerosis: a case-control study. Eur J Neurol 2016; 23: 1308-1321.
2. Mirza A, Forbes JD, Zhu F, Bernstein CN, Van Domselaar G, Graham M, et al. The multiple sclerosis gut microbiota: a systematic review. Mult Scler Relat Disord 2020; 37: 101427.
3. Goodin DS. The epidemiology of multiple sclerosis: insights to a causal cascade. Handb Clin Neurol 2016; 138: 173-206.
4. Calvo-Barreiro L, Eixarch H, Montalban X, Espejo C. Combined therapies to treat complex diseases: the role of the gut microbiota in multiple sclerosis. Autoimmun Rev 2018; 17: 165-174.
5. Rothhammer V, Mascanfroni ID, Bunse L, Takenaka MC, Kenison JE, Mayo L, et al. Type I interferons and microbial metabolites of tryptophan modulate astrocyte activity and central nervous system inflammation via the aryl hydrocarbon receptor. Nat Med 2016; 22: 586-597.
6. Budhram A, Parvathy S, Kremenchutzky M, Silverman M. Breaking down the gut microbiome composition in multiple sclerosis. Mult Scler 2017; 23: 628-636.
7. Ma Q, Xing C, Long W, Wang HY, Liu Q, Wang RF. Impact of microbiota on central nervous system and neurological diseases: the gut-brain axis. J Neuroinflammation 2019; 16: 53.
8. Hill-Burns EM, Debelius JW, Morton JT, Wissemann WT, Lewis MR, Wallen ZD, et al. Parkinson's disease and parkinson's disease medications have distinct signatures of the gut microbiome. Mov Disord 2017; 32: 739-749.
9. Pulikkan J, Maji A, Dhakan DB, Saxena R, Mohan B, Anto MM, et al. Gut microbial dysbiosis in Indian children with autism spectrum disorders. Microb Ecol 2018; 76: 1102-1114.
10. Chen J, Chia N, Kalari KR, Yao JZ, Novotna M, Paz Soldan MM, et al. Multiple sclerosis patients have a distinct gut microbiota compared to healthy controls. Sci Rep 2016; 6: 28484.
11. Miyake S, Kim S, Suda W, Oshima K, Nakamura M, Matsuoka T, et al. Dysbiosis in the gut microbiota of patients with multiple sclerosis, with a striking depletion of species belonging to clostridia XIVa and IV clusters. PLoS One 2015; 10(9): e0137429.
12. Jangi S, Gandhi R, Cox LM, Li N, von Glehn F, Yan R, et al. Alterations of the human gut microbiome in multiple sclerosis. Nat Commun 2016; 7: 12015.
13. Haghikia A, Jörg S, Duscha A, Berg J, Manzel A, Waschbisch A, et al. Dietary fatty acids directly impact central nervous system autoimmunity via the small intestine. Immunity 2015; 43: 817-829.
14. Labbe A, Ganopolsky JG, Martoni CJ, Prakash S, Jones ML. Bacterial bile metabolising gene abundance in Crohn's, ulcerative colitis and type 2 diabetes metagenomes. PLoS One 2014; 9(12): e115175.
15. Thompson AJ, Banwell BL, Barkhof F, Carroll WM, Coetzee T, Comi G, et al. Diagnosis of multiple sclerosis: 2017 revisions of the McDonald criteria. Lancet Neurol 2018; 17: 162-173.
16. Leocani L, Rovaris M, Boneschi FM, Medaglini S, Rossi P, Martinelli V, et al. Multimodal evoked potentials to assess the evolution of multiple sclerosis: a longitudinal study. J Neurol Neurosurg Psychiatry 2006; 77: 1030-1035.
17. Pirker A, Stockenhuber A, Remely M, Harrant A, Hippe B, Kamhuber C, et al. Effects of antibiotic therapy on the gastrointestinal microbiota and the influence of Lactobacillus casei. Food Agric Immunol 2013; 24: 315-330.
18. Png CW, Linden SK, Gilshenan KS, Zoetendal EG, McSweeney CS, Sly LI, et al. Mucolytic bacteria with increased prevalence in IBD mucosa augment in vitro utilization of mucin by other bacteria. Am J Gastroenterol 2010; 105: 2420-2428.
19. Dridi B, Henry M, El Khechine A, Raoult D, Drancourt M. High prevalence of Methanobrevibacter smithii and Methanosphaera stadtmanae detected in the human gut using an improved DNA detection protocol. PLoS One 2009; 4(9): e7063.
20. Collado MC, Derrien M, Isolauri E, de Vos WM, Salminen S. Intestinal integrity and Akkermansia muciniphila, a mucin-degrading member of the intestinal microbiota present in infants, adults, and the elderly. Appl Environ Microbiol 2007; 73: 7767-7770.
21. Gałecka M, Szachta P, Bartnicka A, Łykowska-Szuber L, Eder P, Schwiertz A. Faecalibacterium prausnitzii and Crohn’s disease–is there any connection? Pol J Microbiol 2013; 62: 91-95.
22. Remely M, Dworzak S, Hippe B, Zwielehner J, Aumüller E, Brath H, et al. Abundance and diversity of microbiota in type 2 diabetes and obesity. J Diabetes Metab 2013; 4: 253.
23. Rose'Meyer RB, Mellick AS, Garnham BG, Harrison GJ, Massa HM, Griffiths LR. The measurement of adenosine and estrogen receptor expression in rat brains following ovariectomy using quantitative PCR analysis. Brain Res Brain Res Protoc 2003; 11: 9-18.
24. Rutledge RG, Côté C. Mathematics of quantitative kinetic PCR and the application of standard curves. Nucleic Acids Res 2003; 31: e93.
25. Ghaderian S, Shomali N, Behravesh S, Danbaran GR, Hemmatzadeh M, Aslani S, et al. The emerging role of lncRNAs in multiple sclerosis. J Neuroimmunol 2020; 347: 577347.
26. Waubant E, Lucas R, Mowry E, Graves J, Olsson T, Alfredsson L, et al. Environmental and genetic risk factors for MS: an integrated review. Ann Clin Transl Neurol 2019; 6: 1905-1922.
27. Goldenberg MM. Multiple sclerosis review. P T 2012; 37: 175-184.
28. Lavasani S, Dzhambazov B, Nouri M, Fak F, Buske S, Molin G, et al. A novel probiotic mixture exerts a therapeutic effect on experimental autoimmune encephalomyelitis mediated by IL-10 producing regulatory T cells. PLoS One 2010; 5(2): e9009.
29. Cantarel BL, Waubant E, Chehoud C, Kuczynski J, DeSantis TZ, Warrington J, et al. Gut microbiota in multiple sclerosis: possible influence of immunomodulators. J Investig Med 2015; 63: 729-734.
30. Cosorich I, Dalla-Costa G, Sorini C, Ferrarese R, Messina MJ, Dolpady J, et al. High frequency of intestinal TH17 cells correlates with microbiota alterations and disease activity in multiple sclerosis. Sci Adv 2017; 3(7): e1700492.
31. Wang Y, Yin Y, Chen X, Zhao Y, Wu Y, Li Y, et al. Induction of intestinal Th17 cells by flagellins from segmented filamentous bacteria. Front Immunol 2019; 10: 2750.
32. Tremlett H, Fadrosh DW, Faruqi AA, Hart J, Roalstad S, Graves J, et al. Gut microbiota composition and relapse risk in pediatric MS: a pilot study. J Neurol Sci 2016; 363: 153-157.
33. Korkina L, Kostyuk V, De Luca C, Pastore S. Plant phenylpropanoids as emerging anti-inflammatory agents. Mini Rev Med Chem 2011; 11: 823-835.
34. Schogor AL, Huws SA, Santos GT, Scollan ND, Hauck BD, Winters AL, et al. Ruminal Prevotella spp. may play an important role in the conversion of plant lignans into human health beneficial antioxidants. PLoS One 2014; 9(4): e87949.
35. Moussa L, Bezirard V, Salvador-Cartier C, Bacquie V, Lencina C, Leveque M, et al. A low dose of fermented soy germ alleviates gut barrier injury, hyperalgesia and faecal protease activity in a rat model of inflammatory bowel disease. PLoS One 2012; 7(11): e49547.
36. Leiva-Gea I, Sanchez-Alcoholado L, Martin-Tejedor B, Castellano-Castillo D, Moreno-Indias I, Urda-Cardona A, et al. Gut microbiota differs in composition and functionality between children with Type 1 diabetes and MODY2 and healthy control subjects: a case-control study. Diabetes Care 2018; 41: 2385-2395.
37. den Besten G, van Eunen K, Groen AK, Venema K, Reijngoud DJ, Bakker BM. The role of short-chain fatty acids in the interplay between diet, gut microbiota, and host energy metabolism. J Lipid Res 2013; 54: 2325-2340.
38. Wisniewski PJ, Dowden RA, Campbell SC. Role of dietary lipids in modulating inflammation through the gut microbiota. Nutrients 2019; 11: 117.
39. Gevers D, Kugathasan S, Denson LA, Vázquez-Baeza Y, Van Treuren W, Ren B, et al. The treatment-naive microbiome in new-onset Crohn’s disease. Cell Host Microbe 2014; 15: 382-392.
40. Chu F, Shi M, Lang Y, Shen D, Jin T, Zhu J, et al. Gut microbiota in multiple sclerosis and experimental autoimmune encephalomyelitis: current applications and future perspectives. Mediators Inflamm 2018; 2018: 8168717.
41. Jeraldo P, Hernandez A, Nielsen HB, Chen X, White BA, Goldenfeld N, et al. Capturing one of the human gut microbiome’s most wanted: reconstructing the genome of a novel butyrate-producing, clostridial scavenger from metagenomic sequence data. Front Microbiol 2016; 7: 783.
42. Tremlett H, Fadrosh DW, Faruqi AA, Zhu F, Hart J, Roalstad S, et al. Gut microbiota in early pediatric multiple sclerosis: a case-control study. Eur J Neurol 2016; 23: 1308-1321.
| Files | ||
| Issue | Vol 13 No 5 (2021) | |
| Section | Original Article(s) | |
| DOI | https://doi.org/10.18502/ijm.v13i5.7428 | |
| Keywords | ||
| Gut microbiota; Relapsing remitting multiple sclerosis; Egypt | ||
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How to Cite
1.
Elgendy S, Abd-Elhameed R, Daef E, Mohammed S, Hassan H, El-Mokhtar M, Nasreldein A, Khedr E. Gut microbiota in forty cases of egyptian relapsing remitting multiple sclerosis. Iran J Microbiol. 2021;13(5):632-641.
