Gut microbiota links with cognitive impairment in amyotrophic lateral sclerosis

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I am not sure of the value of this study, yet as it is well known that a bile acid (TUDCA) may have benefits in ALS, so every story making a connection between bile acids and ALS may be of interest.

Recent studies suggest that the bile acid metabolism is associated with cognitive function.

Cognitive impairments and behavioral abnormalities in 35% of patients with amyotrophic lateral sclerosis (ALS) have been reported. However, the underlying mechanisms have been poorly understood. Mutations in the C9orf72 gene explain the association between ALS and frontotemporal dementia. About 5%–15% of Western ALS patients satisfy the diagnostic criteria for frontotemporal dementia. An intriguing fact is that this C9orf72 mutation barely occurs in Chinese ALS patients, yet about 40% of Chinese ALS patients exhibited CI and that 30% had behavioral abnormalities.

In the current study, the authors explored the role of gut microbiota in cognitive impairment of ALS patients. They collected fecal samples from 35 ALS patients and 35 healthy controls. The scientists analyzed these samples by using 16S rRNA gene sequencing as well as both untargeted and targeted (bile acids) metabolite mapping between patients with cognitive impairment and patients with normal cognition.

They found altered gut microbial communities and a lower ratio of Firmicutes/ Bacteroidetes in the cognitive impairment group, compared with the normal cognition group. In addition, the untargeted metabolite mapping revealed that 26 and 17 metabolites significantly increased and decreased, respectively, in the cognitive impairment group, compared with the normal cognition group.

These metabolites were mapped to the metabolic pathways associated with bile acids. They further found that cholic acid and chenodeoxycholic acid were significantly lower in the cognitive impairment group than in the normal cognition group. Chenodeoxycholic acid and cholic acid are the two primary bile acids in humans.

As primary bile acids move from the small intestine to the colon, they are converted to secondary bile acides (including TUDCA) by the biotransformation of the resident microbial community. So bile acids changes may be associated with a microbiome change in ALS patients.

Bile acids are essential products of cholesterol metabolism. Apolipoprotein E (Apo-E) is a protein involved in the metabolism of fats in the body of mammals. A subtype is implicated in Alzheimer's disease and cardiovascular disease. Similarly a defect in lipid (cholesterol) metabolism may induce cognitive changes. But this is still highly hypothetical.

In conclusion, the authors found that the gut microbiota and its metabolome profile differed between ALS patients with and without cognitive impairment and that the altered bile acid profile in fecal samples was significantly associated with cognitive impairment in ALS patients.

These results need to be replicated in larger studies in the future.

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