Effects of Electroacupuncture Combined with Chinese Herbal Medicine on Gut Microbiota and Metabolomics in Amyotrophic Lateral Sclerosis: A Prospective Study

Abstract

Background and objectives: Recent studies have highlighted a link between amyotrophic lateral sclerosis (ALS) and gut microbiota. This prospective study aimed to evaluate the effects of electroacupuncture combined with Chinese herbal medicine on gut microbiota and metabolomics in ALS patients.

Methods: Ten ALS patients were randomly assigned to either a treatment group (electroacupuncture with Chinese herbal medicine, n = 6) or a control group (waiting treatment, n = 4). Healthy controls (age- and sex-matched, n = 10) were also included. Data were collected after 12 sessions of electroacupuncture and follow-ups at three and six months. ALS functional rating scale scores were documented pre- and post-treatment. Stool samples were collected at two time points (T0 and T4 weeks) and analyzed, and metabolomic profiles from urine samples were analyzed post-treatment. Heatmap correlation analysis was used to explore relationships between microbiota, metabolomics, and clinical outcomes.

Results: Treatment with electroacupuncture reduced Eisenbergiella abundance in the treatment group. A significant positive correlation was found between Lachnospiraceae and ALS functional rating scale scores (P < 0.005 and P < 0.001, respectively). Differential expression of purine metabolism was observed in ALS patients (P = 0.0017).

Conclusions: Imbalances in the gut microbiome and metabolic disorders have been found among patients with ALS. These imbalances appear to be partially mitigated by treatment with electroacupuncture combined with Chinese herbal medicine. Our research suggests that Eisenbergiella might be a diagnostic biomarker and a potential therapeutic target for ALS.

Keywords

Amyotrophic lateral sclerosis / Electroacupuncture / Effect / Gut microbiota / Metabolomics study / Chinese herbal medicine

References

[1] Feldman EL, Goutman SA, Petri S, Mazzini L, Savelieff MG, Shaw PJ, et al. Amyotrophic lateral sclerosis. Lancet 2022;400(10360):1363-1380. doi:10.1016/S0140-6736(22)01272-7, PMID:36116464.

[2] Wolfson C, Gauvin DE, Ishola F, Oskoui M. Global Prevalence and Incidence of Amyotrophic Lateral Sclerosis: A Systematic Review. Neurology 2023; 101(6):e613-e623. doi:10.1212/WNL.0000000000207474, PMID:37308302.

[3] Meyer T. [ Amyotrophic lateral sclerosis (ALS) - diagnosis, course of disease and treatment options]. Dtsch Med Wochenschr 2021; 146(24- 25):1613-1618. doi:10.1055/a-1562-7882, PMID:34879411.

[4] Montiel-Troya M, Mohamed-Mohamed H, Pardo-Moreno T, González-Díaz A, Ruger-Navarrete A, de la Mata Fernández M, et al. Advancements in Pharmacological Interventions and Novel Therapeutic Approaches for Amyotrophic Lateral Sclerosis. Biomedicines 2024; 12(10):2200. doi:10.3390/biomedicines12102200, PMID:39457513.

[5] Yang X, Wang T. Visual Analysis of Research Hotspots in Amyotrophic Lateral Sclerosis based on Bibliometrics. Future Integr Med 2023; 2(3):168-178. doi:10.14218/FIM.2023.00019.

[6] Wang T, Yang X, Du R, Zheng S, Cui H. Acupuncture in the Treatment of Amyotrophic Lateral Sclerosis: A Research Progress in Clinical Trials. Altern Ther Health Med 2023; 29(7):114-118. PMID:37632964.

[7] Lee A, Henderson R, Aylward J, McCombe P. Gut Symptoms, Gut Dysbiosis and Gut-Derived Toxins in ALS. Int J Mol Sci 2024; 25(3):1871. doi:10.3390/ijms25031871, PMID:38339149.

[8] Gong ZX, Ding FF, Ba L, Wen MM, Tang JH, Huang LF, et al. Research progress of intestinal flora in amyotrophic lateral sclerosis. Nerve Injury and Functional Reconstruction 2021; 16(1):29-32. doi:10.16780/j.cnki.sjssgncj.20200433.

[9] Zou X, Shi Y, Zhang T, Huang A, Cui H, Wang T. Electroacupuncture Combined with Chinese Herbal Medicine, Qidong Huoluo Granule, for Amyotrophic Lateral Sclerosis:An 8-Month Case Report. Altern Ther Health Med 2024:AT10994. PMID:38758158.

[10] Wang TQ, Liang TY, Yang XD, Shahrokhi SM, Cui H.Electroacupuncture with combined Chinese herbal, Qidong Huoluo granule for Amyotrophic Lateral Sclerosis:A 9-month Case Report. Hum Biol 2024; 94(4):701-705.

[11] Nicholson JK, Lindon JC, Holmes E. ‘Metabonomics’: understanding the metabolic responses of living systems to pathophysiological stimuli via multivariate statistical analysis of biological NMR spectroscopic data. Xenobiotica 1999; 29(11):1181-1189. doi:10.1080/004982599238047, PMID:10598751.

[12] Fomenko MV, Yanshole LV, Tsentalovich YP. Stability of Metabolomic Content during Sample Preparation: Blood and Brain Tissues. Metabolites 2022; 12(9):811. doi:10.3390/metabo12090811, PMID:36144215.

[13] Xu XJ, Yang Q, Liu ZY, Zhang R, Yu H, Wang ML, et al. Integrative analysis of metabolomics and proteomics unravels purine metabolism dysregulation in the SOD1G93A mouse model of amyotrophic lateral sclerosis. Neurobiol Dis 2023;181:106110. doi:10.1016/j. nbd.2023.106110.

[14] Xu X, Yang Q, Liu Z, Zhang R, Yu H, Wang M, et al. Integrative analysis of metabolomics and proteomics unravels purine metabolism dysregulation in the SOD1(G93A) mouse model of amyotrophic lateral sclerosis. Neurobiol Dis 2023;181:106110. doi:10.1016/j. nbd.2023.106110, PMID:37001614.

[15] Wang TQ, Li LR, Tan CX, Yang JW, Shi GX, Wang LQ, et al. Effect of Electroacupuncture on Gut Microbiota in Participants With Knee Osteoarthritis. Front Cell Infect Microbiol 2021;11:597431. doi:10.3389/ fcimb.2021.597431, PMID:34671567.

[16] Zhou RQ, Liang TY, Zhang YW, Cui H, Wang TQ. Research on the compatibility rule of acupoints in acupuncture treatment of amyotrophic lateral sclerosis. Capital Food and Medicine 2025; 2(1):8-12.

[17] Kania K, Ambrosius W, Kozubski W, Kalinowska-Łyszczarz A. The impact of disease modifying therapies on cognitive functions typically impaired in multiple sclerosis patients: a clinician’s review. Front Neurol 2023;14:1222574. doi:10.3389/fneur.2023.1222574, PMID:37503514.

[18] Xing XL, Qu Y, Xin GL, Zhou HC, Kong Y. Effect analysis of traditional Chinese medicine integrated rehabilitation technology based on acupuncture therapy on limb muscle strength and motor function of stroke patients with hemiplegia. Chinese Archives of Traditional Chinese Medicine 2023; 42(4):69-73. doi:10.13193/j.issn.1673-7717.2024.04.015.

[19] Liao Y, He S, Liu D, Gu L, Chen Q, Yang S, et al. The efficacy and safety of Chinese herbal medicine as an add-on therapy for amyotrophic lateral sclerosis: An updated systematic review and meta-analysis of randomized controlled trials. Front Neurol 2022;13:988034. doi:10.3389/fneur.2022.988034, PMID:36277914.

[20] Wang WB, Zhou YX, Wang Q, Zhu J. Relationship between intestinal flora and amyotrophic lateral sclerosis. Chin J Microecol 2022; 34(5):604-607+612. doi:10.13381/j.cnki.cjm.202205022.

[21] Magrone T, Jirillo E. The interaction between gut microbiota and agerelated changes in immune function and inflammation. Immun Ageing 2013; 10(1):31. doi:10.1186/1742-4933-10-31, PMID:23915308.

[22] Shoemark DK, Allen SJ. The microbiome and disease: reviewing the links between the oral microbiome, aging, and Alzheimer’s disease. J Alzheimers Dis 2015; 43(3):725-738. doi:10.3233/JAD-141170, PMID:25125469.

[23] Miller LE, Lehtoranta L, Lehtinen MJ. The Effect of Bifidobacterium animalis ssp. lactis HN019 on Cellular Immune Function in Healthy Elderly Subjects: Systematic Review and Meta-Analysis. Nutrients 2017; 9(3):191. doi:10.3390/nu9030191, PMID:28245559.

[24] Astbury S, Atallah E, Vijay A, Aithal GP, Grove JI, Valdes AM. Lower gut microbiome diversity and higher abundance of proinflammatory genus Collinsella are associated with biopsy-proven nonalcoholic steatohepatitis. Gut Microbes 2020; 11(3):569-580. doi:10.1080/19 490976.2019.1681861, PMID:31696774.

[25] Kelly CJ, Zheng L, Campbell EL, Saeedi B, Scholz CC, Bayless AJ, et al. Crosstalk between Microbiota-Derived Short-Chain Fatty Acids and Intestinal Epithelial HIF Augments Tissue Barrier Function. Cell Host Microbe 2015; 17(5):662-671. doi:10.1016/j.chom.2015.03.005, PMID: 25865369.

[26] Zhang R, Lao L, Ren K, Berman BM. Mechanisms of acupuncture-electroacupuncture on persistent pain. Anesthesiology 2014; 120(2):482-503. doi:10.1097/ALN.0000000000000101, PMID:24322588.

[27] Chen T, Long W, Zhang C, Liu S, Zhao L, Hamaker BR. Fiber-utilizing capacity varies in Prevotella- versus Bacteroides-dominated gut microbiota. Sci Rep 2017; 7(1):2594. doi:10.1038/s41598-017-02995-4, PMID:28572676.

[28] De Filippo C, Cavalieri D, Di Paola M, Ramazzotti M, Poullet JB, Massart S, et al. Impact of diet in shaping gut microbiota revealed by a comparative study in children from Europe and rural Africa. Proc Natl Acad Sci U S A 2010; 107(33):14691-14696. doi:10.1073/ pnas.1005963107, PMID:20679230.

[29] Du Y, Chen CP, Tseng CY, Eisenberg Y, Firestein BL. Astroglia-mediated effects of uric acid to protect spinal cord neurons from glutamate toxicity. Glia 2007; 55(5):463-472. doi:10.1002/glia.20472, PMID:17203476.

[30] Sayre LM, Perry G, Smith MA. Oxidative stress and neurotoxicity. Chem Res Toxicol 2008; 21(1):172-188. doi:10.1021/tx700210j, PMID:18052107.

[31] Yu ZF, Bruce-Keller AJ, Goodman Y, Mattson MP. Uric acid protects neurons against excitotoxic and metabolic insults in cell culture, and against focal ischemic brain injury in vivo. J Neurosci Res 1998;53(5):613-625. doi:10.1002/(SICI)1097-4547(19980 901)53:5<613::AID-JNR11>3.0.CO;2-1, PMID:9726432.

[32] Wilkinson DJ, Rodriguez-Blanco G, Dunn WB, Phillips BE, Williams JP, Greenhaff PL, et al. Untargeted metabolomics for uncovering biological markers of human skeletal muscle ageing. Aging (Albany NY) 2020; 12(13):12517-12533. doi:10.18632/aging.103513, PMID:32580166.

[33] Cai FF, Ding Y, Fan DL, Zhang Y, Liu SM, Zhao Y. Clinical Effect of Acupuncture Combined with Exercise on Amyotrophic Lateral Sclerosis. World Journal of Integrated Chinese and Western Medicine 2023; 18(1):137-141. doi:10.13935/j.cnki.sjzx.230123.