A homeostasis of the second genome, i.e the gut microbiome is gaining significance as an important phenomenon with relevance to neurological illnesses, because of their influence through the gut brain axis [1]. To maintain the homeostasis, enormous molecular inputs are required as well as the exact nature and a relationship among multitudes of organisms and their complexities is at this point of time is not fully available. However, there have been evidences gathering through the literature on their association of specific organisms whose good or bad influence on neurological illnesses is being deciphered. One such organism of significance has been the Enterobacteriaceae whose curli-production leads to α-synuclein misfolding and accumulation which has been found to be a key factor driving the pathogenesis of neurodevelopmental conditions such as autism spectrum disorder (ASD) and neuro-degenerative conditions such as Parkinson's and Alzheimer's disease [2,3]. In a study on children with ASD, we have been able to control the abundance of Enterobacteriaceae using a biological response modifier beta glucan (BRMG) [4]. In addition to that beneficial bacteria such as Faecalibacterium prausnitzii and Prevotella copri have been found to be increased. This study has two important milestones of achievement,
i. There have been no reports in the literature to our knowledge proving that harmful bacteria such as Enterobacteriaceae can be controlled using an orally consumed food supplement, the black yeast Aureobasidium pullulans AFO-strain produced BRMG.
ii. To populate beneficial bacteria as a therapeutic strategy for diseases and disorders, two major approaches are probiotic based or fecal microbiota transplantation (FMT) [5]; However, our study uses a prebiotic approach that regulates the gut dysbiosis apart from beneficial influence on the associated immune parameters as well.
This BRMGs have been in consumption as a food supplement from the 90s and it is produced in a GMP facility and its safety has been proven apart from it not containing any of the notified allergens [6]. In the above study the correlation of correction of dysbiosis with improvement in sleep and behaviour pattern make us recommend studies using this BRMG for other amyloidosis based neurodevelopmental and neurodegenerative (Parkinson's, Alzheimer's disease etc.,)
[4]
In another pre-clinical study on a Stellic Animal Model (STAM) of non-alcoholic steatohepatitis (NASH) [7], the AFO-202 beta glucan the decrease in the abundance of Enterobacteriaceae, other Firmicutes were highest in the AFO-202 group while inflammation associated bacteria such as Turicibacter and A. muciniphila were highest in another group which was administred A.pullulans N-163 strain produced BRMG. On these lines, it is worthwhile to note that a clinical trial is ongoing for evaluating the efficacy of the N-163 BRMG against neuro-inflammation and regulation of gut dysbiosis in patients with multiple-sclerosis [8]. Increase in Bacteroides and lactobacillus was highest in the AFO-202+N-163 group in the NASH study. Lactobacillus is a widely used pro-biotic and the increase in Bacteroides which has been reported to be of help in life-style metabolic disorders [9] and chronic conditions such as cancer apart for healthy aging makes these BRMGs as an ideal approach to the management of several diseases and disorders as adjuncts to existing treatments.
References:
-
1.Carabotti M, Scirocco A, Maselli MA, Severi C. The gut-brain axis: interactions between enteric microbiota, central and enteric nervous systems. Ann Gastroenterol. 2015 Apr-Jun;28((2)):203–209. [PMC free article] [PubMed] [Google Scholar]
-
2.Sampson TR, Challis C, Jain N, Moiseyenko A, Ladinsky MS, Shastri GG, Thron T, Needham BD, Horvath I, Debelius JW, Janssen S, Knight R, Wittung-Stafshede P, Gradinaru V, Chapman M, Mazmanian SK. A gut bacterial amyloid promotes α-synuclein aggregation and motor impairment in mice. Elife. 2020 Feb 11;9:e53111. doi: 10.7554/eLife.53111. [DOI] [PMC free article] [PubMed] [Google Scholar]
-
3.Scheperjans F, Aho V, Pereira PA, Koskinen K, Paulin L, Pekkonen E, Haapaniemi E, Kaakkola S, Eerola-Rautio J, Pohja M, Kinnunen E, Murros K, Auvinen P. Gut microbiota are related to Parkinson's disease and clinical phenotype. Mov Disord. 2015 Mar;30((3)):350–8. doi: 10.1002/mds.26069. [DOI] [PubMed] [Google Scholar]
-
4.Raghavan K, Dedeepiya VD, Yamamoto N, Ikewaki N, Sonoda T, Iwasaki M, Kandaswamy R, Senthilkumar R, Preethy S, Abraham SJK. Benefits of gut microbiota reconstitution by beta 1,3-1,6 glucans in subjects with autism spectrum disorder and other neurodegenerative diseases. Journal of Alzheimer's Disease. Jan. 1, 2022. pp. 1–12. [DOI] [PMC free article] [PubMed]
-
5.Li N, Chen H, Cheng Y, Xu F, Ruan G, Ying S, Tang W, Chen L, Chen M, Lv L, Ping Y, Chen D, Wei Y. Fecal Microbiota Transplantation Relieves Gastrointestinal and Autism Symptoms by Improving the Gut Microbiota in an Open-Label Study. Front Cell Infect Microbiol. 2021 Oct 19;11:759435. doi: 10.3389/fcimb.2021.759435. [DOI] [PMC free article] [PubMed] [Google Scholar]
-
6.www.nichiglucan.com
-
7.Preethy S, Ikewaki N, Levy GA, Raghavan K, Dedeepiya VD, Yamamoto N, Srinivasan S, Ranganathan N, Iwasaki M, Senthilkumar R, Abraham SJK. Two unique biological response-modifier glucans beneficially regulating gut microbiota and faecal metabolome in a non-alcoholic steatohepatitis animal model, with potential for applications in human health and disease. BMJ Open Gastroenterology. 2022;9:e000985. doi: 10.1136/bmjgast-2022-000985. [DOI] [PMC free article] [PubMed] [Google Scholar]
-
8.http://ctri.nic.in/Clinicaltrials/pdf_generate.php?trialid=69004
-
9.Aggarwal J, Swami G, Kumar M. Probiotics and their Effects on Metabolic Diseases: An Update. J Clin Diagn Res. 2013 Jan;7((1)):173–7. doi: 10.7860/JCDR/2012/5004.2701. [DOI] [PMC free article] [PubMed] [Google Scholar]