Biofactory in the intestine
Genetically modified microbiota will help improve immunity
Daria Spasskaya, N+1
One of the species of bacteria inhabiting the intestine decomposes aromatic amino acids to form many metabolites, nine of which accumulate in the host's blood serum. Researchers from Stanford Medical School have demonstrated that the amount of at least one of them – indolpropionic acid – can be changed by gene modification of bacteria. As scientists have shown in their work published in Nature, the concentration of indolpropionic acid in the blood of mice affects the composition of immune cells (Dodd et al., A gut bacterial pathway metabolizes aromatic amino acids into nine circulating metabolites).
We have already told more than once that the intestinal microbiota is able to modulate the host's immunity. Bacteria turn food components into biologically active substances that affect the activity of immune cells in different ways.
A research team from Stanford and the University of California, led by Michael A. Fischbach, showed that the number of immune cells that determine both innate and acquired immunity varies depending on the concentration of indolpropionic acid (IPC). It has previously been shown that this substance has antioxidant and neuroprotective effects.
Scientists have discovered that indolpropionic acid is formed from the amino acid tryptophan, which comes from food as a result of the activity of the intestinal bacterium Clostridium sporogenes. It was known that clostridia are able to metabolize other aromatic amino acids – phenylalanine and tyrosine – to similar compounds involving the enzyme phenylactate dehydratase (Fld). The researchers suggested that the same enzyme participates in the metabolism of tryptophan with the formation of indolpropionic acid.
In order to test this, scientists turned off the fldC gene encoding one of the enzyme subunits in C.sporogenes. The concentration of metabolites in the culture medium was determined using gas chromatography combined with mass spectrometry. The production of IPK in the culture of mutant bacteria has really disappeared.
After the intestines of sterile mice were populated with mutant and normal C.sporogenes bacteria, the concentration of IPC in the blood serum of control individuals was about 80 micromoles, it was not detected in the blood of mice with mutant bacteria. But in the peripheral blood of animals, the number of both mature T cells (helper cells and cytotoxic lymphocytes) and neutrophils and macrophages, cells of the innate immune response, increased.
In total, with the participation of an enzyme from aromatic amino acids, 12 different compounds can be obtained, nine of which accumulate in the blood serum, and probably somehow affect the work of the body. The authors suggest that genetic engineering of intestinal bacteria is a promising way to specifically modulate the content of certain metabolites in the body and thereby influence the host's immunity.
Earlier, researchers from the University of Washington School of Medicine found that an increase in the amount of deaminothyrosine, another metabolite of aromatic compounds that is produced by another type of intestinal clostridium, protected mice from pneumonia with influenza.
The metabolite formed with the participation of the microorganism Clostridium orbiscindens stimulates an interferon-dependent immune response that protects the host from complications of infection. Perhaps a diet enriched with flavonoids will help to enhance the production of the metabolite by microbes.
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