Abnormal Gut Microflora

Besides of the two normal types of gut microflora shown before, animals not fealing well (for example due to toxic side effects of drugs) can show abnormal deviations from the two normal patterns of gut microflora. In the figure below, samples from the competitive study are shown (non-dosed samples, low-dosed with compound B and high-dosed with compound B). It is visible that besides of the two normal types of gut microflora such as the high-Hippurate type (low levels of trans-2-Hydroxycinnamate and 3-Hdyroxyphenylpropanoate) and the low-Hippurate type (high levels of trans-2-Hydroxycinnamate and 3-Hdyroxyphenylpropanoate), a third abnormal type of gut microflrora is visible for low-dosed and high-dosed animals (starting 24h after dosing), which is characterized by low levels of all three metabolites in urine. This type, which is also visible for animals treated with antibiotic agents and for germ-free animals, corresponds to a break-down of gut microflora. This is a sensitive and early indicator that the animals are not feeling well (similarily, nearly everybody of us has already had experience with the sensitivity of the own gut microflora). The discrimination of these three states of gut microflora is only possible if the patterns of all three metabolites are investigated in a multivariate way and not by monitoring single metabolites in a univariate way. In additeon other metabolites such as Phenylacetylglycine are influenced by the gut microflora. As these metabolites are also indicators for other effects (for example monitoring phospholipidosis), it is obvious that in the field of metabonomics it is highly important to look at changes of as many metabolites and not only at single metabolites.

Urine samples of a competitive study with control animals and animals dosed by compound B. The samples are colored by dose (green = control sample, red = low-dosed sample and black = high-dosed samples). Besides of the normal high-Hippurate type and the low-Hippurate type a third type of gut microflrora is visible for low-dosed and high-dosed animals (starting 24h after dosing), which is characterized by low levels of all three metabolites in urine.