Analysis of gut microbiota in patients with cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL)

Abstract

Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is a major hereditary small vessel disease caused by mutations in NOTCH3. The variations in progression and severity among patients suggest that the CADASIL phenotype is modified by some genetic and environmental factors. Recent studies have shown the potential roles of gut microbiota in human diseases. We hypothesized that gut microbiota modifies the disease phenotype. We performed gut microbial meta 16S rRNA analysis of fecal samples from 15 CADASIL patients and 16 controls. The microbial α and β diversities and taxonomy were compared between CADASIL patients and controls and between CADASIL patients with and without an ischemic stroke history. No signifi cant difference in α or β diversity was observed in either case control or subgroup comparisons. In the taxonomic microbial analysis, there was a significant increase in abundance of 6 genera and significant decrease in 2 genera in CADASIL patients compared with controls. There was a significant decrease in abundance of 2 genera in CADASIL patients with compared with those without stroke. This is the first study on CADASIL focusing on gut micro biota. Our findings suggest that gut microbiota modifies the onset and progression of CADASIL.

Pathophysiological Mechanisms and Potential Therapeutic Targets in Cerebral Autosomal Dominant Arteriopathy With Subcortical Infarcts and Leukoencephalopathy (CADASIL)

“…On the contrary, the association between stroke and body mass index, raised cholesterol, or elevated serum homocysteine was not demonstrated in CADASIL (Adib-Samii et al, 2010). Interestingly, a recent study found significant taxonomic differences in gut microbiota between CADASIL patients and controls, suggesting a possible role of gut microbiota in influencing disease onset and progression, but more research is needed to confirm this hypothesis (Matsuura et al, 2019). The role of cardiovascular risk factors could be particularly important in EGFR 7-34 mutated individuals, who needs additional risk factors for the classical CADASIL phenotype to develop, while mutations in EGFR 1-6 may have a strong enough effect to cause the disease.…”

Contribution of “Omic” Studies to the Understanding of Cadasil. A Systematic Review

“…There is a single study that focuses on the analysis of the microbiome in CADASIL patients, where the gut microbiome of 15 Japanese CADASIL patients and 16 controls was evaluated [ 52 ]. CADASIL patients were divided according to whether they had suffered a symptomatic ischemic stroke ( n = 7) or not ( n = 8).…”

“…There was no significant difference in vascular risk factors or nutritional items between CADASIL patients and the controls. The only significant difference was the daily intake of arachidonic acid between CADASIL subgroups, as patients with stroke had a lower intake ( p = 0.03) [ 52 ].…”

“…A total of 790 operational taxonomic units (OTUs) was detected after the removal of singletons. No significant difference was observed in α-diversity or β-diversity between CADASIL patients and the controls or between the patients with and without stroke [ 52 ].…”

“…In CADASIL patients compared with controls, there was a significant increase in abundance of the following: Lachnospira, Odoribacter, Parvimonas , unclassified genera belonging to Barnesiellaceae and Lachnospiraceae, unclassified genus belonging to order SHA-98; and a significant decrease in: Megasphaera and Acidaminococcus . Regarding the OTU level, CADASIL patients showed a significant increase in abundance of 24 OTUs and a significant decrease in 4 [ 52 ]. Between CADASIL subgroups, those with a stroke had a significant decrease in abundance of Phascolarctobacterium and Paraprevotella , a significant increase in abundance of 13 OTUs, and significant decrease in 3 OTUs [ 52 ].…”