The gut-brain axis filling in the blanks
Summary by Mara Luciana Floare, PhD student, the University of Sheffield
Potential roles of gut microbiome and metabolites in modulating ALS in mice. DOI: 10.1038/s41586-019-1443-5
Eran Blacher, Stavros Bashiardes, Hagit Shapiro, Daphna Rothschild, Uria Mor, Mally Dori-Bachash, Christian Kleimeyer, Claudia Moresi, Yotam Harni, Maya Zur, Michal Zabari, Rotem Ben-Zeev Brik, Denise Kviatcovsky, Niv Zmora, Yotam Cohen, Noam Bar, Izhak Levi, Nira Amar, Tevie Mehlman, Alexander Brandis, Inbal Biton, Yael Kuperman, Michael Tsoory, Leenor Alfahel, Alon Harmelin, Michal Schwartz, Adrian Israelson, Liisa Arike, Malin E V Johansson, Gunnar C Hansson, Marc Gotkine, Eran Segal, Eran Elinav
22 July 2019
Amyotrophic lateral sclerosis (ALS) is a complex disorder which affects the areas of the brain responsible for movement as well as the functioning of internal organs. Environmental factors such as diet, physical activity and exposure to toxins have been suggested to contribute to the development of the disease, possibly through the impact they might have on the population of bacteria that reside in our gut.
The gut bacteria, collectedly referred to as the gut microbiome, represent trillions of bacteria of different species, which can be normally found in our gut and which play an important role in the process of digestion. Through the breakdown of food, these bacteria release various by-products which can impact the biochemical balance of our body and possibly promote health or contribute to disease, depending on each species of bacteria and the molecules they produce. In the paper by Blacher et al (2019), the diversity of the gut microbiome was analysed in animal models of ALS and healthy mice (which represented a control group) and the results indicated that the microbiome of mice in the control group had a greater number of types of bacteria compared to that of mice in the ALS group. Next, the researchers administered antibiotics or water to ALS mice in order to experimentally kill some of the gut bacteria species. The findings indicate that, compared to the ALS mice which received water, the ones treated with antibiotics had significantly worsen disease symptoms.
Next, different types of bacteria were administered to ALS mice pre-treated with antibiotics and to healthy mice (control group), and some strains such as P.distasonis, R.torques, L.gasseri and P.melaninogenics appeared to worsen the progression of the disease whereas A.muciniphila showed beneficial effects, prolonging the survival of ALS mice. Further analysis indicated that A.muciniphila might slow down ALS symptoms through the release of a by-product called nicotinamide, which plays an important role in energy production.
To summarise, the paper by Blacher et al (2019) highlights the involvement of the gut microbiome in the development and progression of ALS. Even though the study is limited by the fact that only one mouse model of ALS was used and just one by-product was investigated in detail out of several that might have implications to ALS as well, these findings open the way to larger, prospective human studies and possibly help identify microbial therapeutic targets.
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