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. 2022 Dec 2:13:1043579.
doi: 10.3389/fimmu.2022.1043579. eCollection 2022.

Hypothesis of a potential BrainBiota and its relation to CNS autoimmune inflammation

Maria L Elkjaer  1   2   3 , Lukas Simon  4 , Tobias Frisch  5 , Lisa-Marie Bente  6   7 , Tim Kacprowski  6   7 , Mads Thomassen  2   8 , Richard Reynolds  9   10 , Jan Baumbach  11 , Richard Röttger  5 , Zsolt Illes  1   2   3
Affiliations

Hypothesis of a potential BrainBiota and its relation to CNS autoimmune inflammation

Maria L Elkjaer et al. Front Immunol. .

Abstract

Infectious agents have been long considered to play a role in the pathogenesis of neurological diseases as part of the interaction between genetic susceptibility and the environment. The role of bacteria in CNS autoimmunity has also been highlighted by changes in the diversity of gut microbiota in patients with neurological diseases such as Parkinson's disease, Alzheimer disease and multiple sclerosis, emphasizing the role of the gut-brain axis. We discuss the hypothesis of a brain microbiota, the BrainBiota: bacteria living in symbiosis with brain cells. Existence of various bacteria in the human brain is suggested by morphological evidence, presence of bacterial proteins, metabolites, transcripts and mucosal-associated invariant T cells. Based on our data, we discuss the hypothesis that these bacteria are an integral part of brain development and immune tolerance as well as directly linked to the gut microbiome. We further suggest that changes of the BrainBiota during brain diseases may be the consequence or cause of the chronic inflammation similarly to the gut microbiota.

Keywords: CNS autoimmunity; bacterial transcripts; brainbiome; brainbiota; gut-brain axis; microbiome; microbiota; smoldering MS.

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Conflict of interest statement

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.

Figures

Figure 1
Figure 1
Distribution of microbes based on transcripts in the healthy brain and MS lesions. (A) Krona plot visualizing the distribution of the different microbes detected in the healthy brain based on RNA sequencing. The figure highlights the presence of three major bacterial phyla. (B) Volcano plot of the distribution of the different microbes represented by the dots based on differential expressed genes in NAWM vs control WM (n=90 transcripts) (left panel) and in active lesion type vs control WM (n=294 transcripts) (right panel). The figure indicates reduced diversity in both the MS NAWM and active lesions with inflammatory activity based on the higher expressed transcripts from different microbes in control WM. (C) Number of microbes significantly changed in the different MS white matter lesion types compared to control WM. Note the most reduced diversity in the active lesions with the highest inflammatory activity. The bacteria and brain are created by Biorender.com.
Figure 2
Figure 2
Hypothesis of the BrainBiota and its role in MS. (A) The healthy brain has a microbiota (BrainBiota). (B) The BrainBiota overlaps with the gut microbiome as it originates from the early gut microbiome. (C) Dysregulated BrainBiota may contribute and maintain chronic inflammation in brain diseases or be the result of the inflammatory milieu.Illustration was created in BioRender.
See this image and copyright information in PMC

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