Lyso-Gb3 modulates the gut microbiota and decreases butyrate production

Parts of this work were previously presented at the 21st, 22nd, and 23rd Spanish Congress of Clinical Microbiology and Infectious Diseases, the 29th European Congress of Clinical Microbiology and Infectious Diseases, the 6th Update on Fabry Disease, and 15th Annual Word Symposium of Lysosomal Diseases Research & Conference.
Fabry disease is a rare X-linked lysosomal storage disorder resulting from deficient activity of α-galactosidase A, leading to the accumulation of glycosphingolipids such as globotriaosylsphingosine (lyso-Gb3). The gastrointestinal symptoms of this disease may be disabling, and the life expectancy of affected patients is shortened by kidney and heart disease. Our hypothesis was that lyso-Gb3 may modify the gut microbiota. The impact of a clinically relevant concentration of lyso-Gb3 on mono- or multispecies bacterial biofilms were evaluated. A complex bacterial community from the simulated transverse colon microbiota was studied using quantitative PCR to estimate different bacterial group concentrations and a HPLC was used to estimate short-chain fatty acids concentrations. We found that lyso-Gb3 increased the biofilm-forming capacity of several individual bacteria, including Bacteroides fragilis and significantly increased the growth of B. fragilis in a multispecies biofilm. Lyso-Gb3 also modified the bacterial composition of the human colon microbiota suspension, increasing bacterial counts of B. fragilis, among others. Finally, lyso-Gb3 modified the formation of short-chain fatty acids, leading to a striking decrease in butyrate concentration. Lyso-Gb3 modifies the biology of gut bacteria, favoring the production of biofilms and altering the composition and short-chain fatty-acid profile of the gut microbiota.
JJAC is funded by an FPI grant from Spanish Ministry of Economics and Competitiveness (BES-2014-069007). The authors were further supported by FIS PI16/02057, PI18/01366, ISCIII-RETIC REDinREN RD016/0009 Fondos FEDER, Sociedad Española de Nefrología, Comunidad de Madrid B2017/BMD-3686 CIFRA2-CM, Miguel Servet MS14/00133 to MDSN and AGL2016-75951-R.