Endogenous Ethanol and Triglyceride Production by Gut Pichia kudriavzevii, Candida albicans and Candida glabrata Yeasts in Non-Alcoholic Steatohepatitis
Babacar Mbaye, Patrick Borentain, Reham Magdy Wasfy, Maryam Tidjani Alou, Nicholas Armstrong, Giovanna Mottola +5 more
Cells
Abstract
Nonalcoholic steatohepatitis (NASH) increases with fructose consumption and metabolic syndrome and has been recently linked with endogenous ethanol production, notably by high alcohol-producing <i>Klebsiella pneumoniae</i> (HiAlc Kpn). <i>Candida</i> yeasts are the main causes of auto-brewery syndromes but have been neglected in NASH. Here, the fecal ethanol and microbial content of 10 cases and 10 controls were compared. Ethanol was measured by gas chromatography-mass spectrometry. Species identification was performed by MALDI-TOF MS, and triglyceride production was assessed by a colorimetric enzymatic assay. The fecal ethanol concentration was four times higher in patients with NASH (median [interquartile range]: 0.13 [0.05-1.43] vs. 0.034 [0.008-0.57], <i>p</i> = 0.037). Yeasts were isolated from almost all cases but not from controls (9/10 vs. 0/10, <i>p</i> = 0.0001). <i>Pichia kudriavzevii</i> was the most frequent (four patients), while <i>Candida glabrata</i>, <i>Candida albicans,</i> and <i>Galactomyces geotrichum</i> were identified in two cases each. The concentration of ethanol produced by yeasts was 10 times higher than that produced by bacteria (median, 3.36 [0.49-5.60] vs. 0.32 [0.009-0.43], <i>p</i> = 0.0029). Using a 10% D-fructose restricted medium, we showed that NASH-associated yeasts transformed fructose in ethanol. Unexpectedly, yeasts isolated from NASH patients produced a substantial amount of triglycerides. <i>Pichia kudriavzevii</i> strains produced the maximal ethanol and triglyceride levels in vitro. Our preliminary human descriptive and in vitro experimental results suggest that yeasts have been neglected. In addition to <i>K. pneumoniae</i>, gut <i>Pichia</i> and <i>Candida</i> yeasts could be linked with NASH pathophysiology in a species- and strain-specific manner through fructose-dependent endogenous alcohol and triglyceride production.