Bacterial uraemic toxins (hippuric acid, p-cresyl sulphate, indole-3-acetic acid)

Bacterial uraemic toxins are substances that gut bacteria make from food components and that the body then converts further in the liver and kidneys. They get their name because they accumulate in the blood when kidney function is reduced (uraemia). They are measured in urine: hippuric acid, HPHPA, indole-3-acetic acid, indoxyl sulphate, p-cresyl sulphate, phenylacetylglutamine and tryptamine. Indoxyl sulphate is described in more detail on the indican page, TMAO on a page of its own. Uraemic toxins are also covered in the capillary blood analysis Prevent 360.

How gut bacteria produce uraemic toxins

When protein reaches the colon undigested, bacteria break down its amino acids. Tyrosine and phenylalanine yield p-cresol, which the gut lining and the liver combine with sulphuric acid to form p-cresyl sulphate. From phenylalanine, bacteria form phenylacetic acid, which is coupled to glutamine in the liver and kidneys – producing phenylacetylglutamine. Tryptophan yields indole, indole-3-acetic acid and tryptamine. Hippuric acid derives mainly from benzoic acid, which bacteria release from polyphenols in fruit, tea and coffee and which the liver links to glycine. HPHPA is associated with the metabolism of certain clostridia. The kidneys excrete most of these substances actively via transporters in the renal tubules; in the blood, many of them are bound to albumin.

High bacterial uraemic toxins – what happens in the body?

High levels of p-cresyl sulphate, phenylacetylglutamine or indoxyl sulphate indicate increased bacterial protein putrefaction. This occurs with a high-protein, low-fibre diet, when stool stays in the gut for a long time or when more undigested protein reaches the colon, for example with lower enzyme output from the pancreas. In cell experiments, p-cresyl sulphate and indoxyl sulphate promote oxidative stress and inflammatory responses in vascular and kidney cells; for phenylacetylglutamine, studies have observed increased activation of blood platelets. Tryptamine stimulates gut movement and fluid secretion in the colon via serotonin receptors. A high hippuric acid value, by contrast, often reflects a diet rich in polyphenols. Raised HPHPA values are associated with increased clostridial activity; their significance is debated.

Low bacterial uraemic toxins – what does it mean?

Low levels of the putrefaction products p-cresyl sulphate, phenylacetylglutamine and indoxyl sulphate show that little protein is broken down by bacteria in the colon – typical of a high-fibre diet, in which bacteria mainly ferment carbohydrates. Low hippuric acid may point to a low intake of polyphenols or to reduced bacterial conversion; studies have observed low urinary hippuric acid together with lower diversity of the gut flora, also after antibiotics. Little indole-3-acetic acid and tryptamine means that bacteria convert little tryptophan into these messengers. Together with indican, skatole and the microbiome analysis, it helps to assess which metabolic pathways of the gut flora predominate.

The interpretation is given in your report.