Reduced Mass and Diversity of the Colonic Microbiome in Patients with Multiple Sclerosis and Their Improvement with Ketogenic Diet

Alexander Swidsinski, Yvonne Dörffel, Vera Loening-Baucke, Christoph Gille, Önder Göktas, Anne Reißhauer, Jürgen Neuhaus, Karsten-Henrich Weylandt, Alexander Guschin, Markus Bock, Alexander Swidsinski, Yvonne Dörffel, Vera Loening-Baucke, Christoph Gille, Önder Göktas, Anne Reißhauer, Jürgen Neuhaus, Karsten-Henrich Weylandt, Alexander Guschin, Markus Bock

Abstract

Background: Colonic microbiome is thought to be involved in auto-immune multiple sclerosis (MS). Interactions between diet and the colonic microbiome in MS are unknown. Methods: We compared the composition of the colonic microbiota quantitatively in 25 MS patients and 14 healthy controls.Fluorescence in situ hybridization (FISH) with 162 ribosomal RNA derived bacterial FISH probes was used. Ten of the MS patients received a ketogenic diet for 6 months. Changes in concentrations of 35 numerically substantial bacterial groups were monitored at baseline and at 2, 12, and 23/24 weeks. Results: No MS typical microbiome pattern was apparent.The total concentrations and diversity of substantial bacterial groups were reduced in MS patients (P < 0.001). Bacterial groups detected with EREC (mainly Roseburia), Bac303 (Bacteroides), and Fprau (Faecalibacterium prausnitzii) probes were diminished the most. The individual changes were multidirectional and inconsistent. The effects of a ketogenic diet were biphasic. In the short term, bacterial concentrations and diversity were further reduced. They started to recover at week 12 and exceeded significantly the baseline values after 23-24 weeks on the ketogenic diet. Conclusions: Colonic biofermentative function is markedly impaired in MS patients.The ketogenic diet normalized concentrations of the colonic microbiome after 6 months.

Keywords: FISH; biofermentation; colonic microbiota; ketogenic diet; multiple sclerosis.

References

    1. Berer K., Krishnamoorthy G. (2014). Microbial view of central nervous system autoimmunity. FEBS Lett. 588, 4207–4213. 10.1016/j.febslet.2014.04.007
    1. Choi I. Y., Piccio L., Childress P., Bollman B., Ghosh A., Brandhorst S., et al. . (2016). A diet mimicking fasting promotes regeneration and reduces autoimmunity and multiple sclerosis symptoms. Cell Rep. 15, 136–146. 10.1016/j.celrep.2016.05.009
    1. Galland L. (2014). The gut microbiome and the brain. J. Med. Food 17, 1261–1272. 10.1089/jmf.2014.7000
    1. Glenn J. D., Mowry E. M. (2016). Emerging concepts on the gut microbiome and multiple sclerosis. J. Interferon Cytokine Res. 36, 347–357. 10.1089/jir.2015.0177
    1. Jangi S., Gandh R., Cox L. M., Li N., von Glehn F., Yan R., et al. . (2016). Alterations of the human gut microbiome in multiple sclerosis. Nat. Commun. 7:12015. 10.1038/ncomms12015
    1. Kim D. Y., Hao J., Liu R., Turner G., Shi F. D., Rho J. M. (2012). Inflammation-mediated memory dysfunction and effects of a ketogenic diet in a murine model of multiple sclerosis. PLoS ONE 7:e35476. 10.1371/journal.pone.0035476
    1. Loy A., Maixner F., Wagner M., Horn M. (2016). ProbeBase—an online resource for rRNA-targeted oligonucleotide probes: new features. Nucleic Acids Res. 35, 800–804. 10.1093/nar/gkv1232
    1. Mai V., Prosperi M., Yaghjyan L. (2016). Moving microbiota research toward establishing causal associations that represent viable targets for effective public health interventions. Ann. Epidemiol. 26, 306–310. 10.1016/j.annepidem.2016.03.011
    1. Miyake S., Kim S., Suda W., Oshima K., Nakamura M., Matsuoka T., et al. . (2015). 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 10:e0137429. 10.1371/journal.pone.0137429
    1. Piccio L., Stark J. L., Cross A. H. (2008). Chronic calorie restriction attenuates experimental autoimmune encephalomyelitis. J. Leukoc. Biol. 84, 940–948. 10.1189/jlb.0208133
    1. Suau A., Rochet V., Sghir A., Gramet G., Brewaeys S., Sutren M., et al. . (2001). Fusobacterium prausnitzii and related species represent a dominant group within the human fecal flora. Syst. Appl. Microbiol. 24, 139–145. 10.1078/0723-2020-00015
    1. Swidsinski A. (2006). Standards for bacterial identification by fluorescence In situ hybridization within eukaryotic tissue using ribosomal rRNA-based probes. Inflamm. Bowel Dis. 12, 824–826.
    1. Swidsinski A., Loening-Baucke V., Kirsch S., Doerffel Y. (2010). Functional biostructure of colonic microbiota in healthy subjects and patients with diarrhea treated with Saccharomyces boulardii. Gastroenterol. Clin. Biol. 34, 79–92. 10.1016/S0399-8320(10)70025-7
    1. Swidsinski A., Loening-Baucke V., Schulz S., Manowsky J., Verstraelen H., Swidsinski S. (2016). Functional anatomy of the colonic bioreactor: impact of antibiotics and Saccharomyces boulardii on bacterial composition in human fecal cylinders. Syst. Appl. Microbiol. 39, 67–75. 10.1016/j.syapm.2015.11.002
    1. Tanca A., Palomba A., Pisanu S., Addis M. F., Uzzau S. (2015). Enrichment or depletion? The impact of stool pretreatment on metaproteomic characterization of the human gut microbiota. Proteomics 15, 3474–3485. 10.1002/pmic.201400573
    1. Tremlett H., Fadrosh D. W., Faruqi A. A., Zhu F., Hart J., Roalstad S., et al. . (2016). Gut microbiota in early pediatric multiple sclerosis: a case-control study. Eur. J. Neurol. 23, 1308–1321. 10.1111/ene.13026

Source: PubMed

Sponsorit ja yhteistyökumppanit

Sairaudet

Huumeiden interventiot

3
Tilaa