Novel In Vitro Intestinal Microbiome Model to Study Lipidomic and Metabolomic Adaptations Due to Exposure to Glyphosate, Perfluorooctanoic Acid, and Docusate Sodium

Cell and animal models have been used to provide insights
with
regard to physiological changes in intestinal flora due to exposure
to drugs and environmental contaminants. Here, a novel in
vitro model known as simulator of the human intestinal microbial
ecosystem (SHIME) was used to assess the effects of three chemicals
of emerging concern, namely glyphosate, perfluorooctanoic acid (PFOA),
and docusate sodium (dioctyl sulfosuccinate, DOSS), on the lipidomic
and metabolomic profiles of the gut microenvironment in both the proximal
and distal colonic compartments. Nontargeted analyses by ultra-high
performance liquid chromatography-tandem mass spectrometry and gas
chromatography–electron ionization-mass spectrometry revealed
minor differences in the lipidomic and metabolomic signatures of the
proximal and distal colon following treatment with either glyphosate
or PFOA at acceptable human daily intake levels or average daily exposures.
However, global dysregulation of lipids and metabolites was observed
due to DOSS treatment at conventional prescription doses when indicated
as a stool softener. Our findings suggest that the current guidelines
for glyphosate and PFOA exposure may be adequate at the level of the
lower gut microbiome in healthy adults, but the probable yet uncharacterized
off-target effects, safety, and efficacy of long-term DOSS treatment
warrants further investigation. Indeed, we highlight the SHIME system
as a novel in vitro approach which can be used as
a screening tool to assess the impact of drugs and/or chemicals on
the gut microbiome, while implementing state-of-the-art and data-driven
mass spectrometric workflows to identify toxic lipidomic and metabolomic
signatures.