For the IMBS patient subgroup, which shows a fecal like body odor, the metabolites indole and secondary skatole are in the focus as those metabolites are creating a strong fecal like scent.
We expect at least three different types of causative reasons in those subgroups:
Enzyme deficiencies in directly indole degrading enzymes like e.g. CYP2E1, CYP2B, ...
Enzyme deficiencies in the choline -> glycine degradation pathway (BHMT2, Methyltetrahydrofolate cluster)
Enzyme deficiencies in the lower glycine + benzoate -> hippurate degradation pathway
Shikimate pathway forming Tryptophan over Indole
The shikimate pathway [1] is a microbial pathway which is responsible for the biosynthesis of tryptophan combining indole and glyine/serine [2] .
As its precursors glycine and serine and the product tryptophan are involved, the human degradation pathways of those amino acids might be of high relevancy for the elevated formation of indole.
Also of high importance are glutamine and glutamate as they are related to the source of the second precursor anthranilate of the indole synthesis.
Choline -> Glycine degradation pathway
A subgroup of fecal body odor patients do show also positive Trimethylaminuria urine tests. Which indicates a formation of elevated Trimethylamine (TMA) levels in the intestinal area. One reason could be a impaired choline uptake and degradation which results in an elevated degradation of choline to TMA in the intestinal lumen. As the degradation pathway of choline also affects the availability of glycine and serine, it is a promising candidate branch to be also responsible for an elevated indole concentration.
For this subgroup folate supplementation might be helpful, as folate supports the choline, betaine -> glycine, serine degradation.
Glycine + Benzoate -> Hippurate degradation pathway
In metabolome analysis results for fecal body odor patients we observed elevated benzoate with at the same time below normal ranges hippurate levels. Glycine levels were normally low but in normal range.
This is related to the glycine detoxification mechanism [3] , which could be impaired in this subgroup of IMBS patients by too low availability of glycine or serine.
If the indication of a too low availability of glycine and serine is correct, the low levels would impair the bile acid salt conjugation with glycine and lower the availability of glycine in the intestinal lumen.
The ration glycine/taurine would shift and the tryptophan formation over indole + glycine might be impaired with the result of elevated indole concentrations in the intestinal lumen.
High Glutamate, Glycine, Ornithine, Citrulline, Tryptophan, Phenylalanine, Tyrosine, Methionine, Taurine, BCAAs, Ammonia and low Arginine, Glutamine, Lysine -> Urea cycle deficiency
Elevations in various amino acids related to the ammonia degradation have been found with transitive hyperammonemia. This indicates the possibility of a second gene defect in the urea cycle pathway being the source of a fecal smell.
CYP enzyme family
Some CYP family enzymes are known to degradate indole to less odorous metabolites.
Examples are:
Those are prominent candidates for enzyme deficiencies that might lead to an impaired indole degradation.
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