The Probiotic Lactobacillus reuteri Preferentially Synthesizes Kynurenic Acid from Kynurenine.

Publisher: MDPI Country of Publication: Switzerland NLM ID: 101092791 Publication Model: Electronic Cited Medium: Internet ISSN: 1422-0067 (Electronic) Linking ISSN: 14220067 NLM ISO Abbreviation: Int J Mol Sci Subsets: MEDLINE

Original Publication: Basel, Switzerland : MDPI, [2000-

Limosilactobacillus reuteri* ; Probiotics*; Animals ; Kynurenine ; Kynurenic Acid ; Amino Acids ; Mammals

The gut-brain axis is increasingly understood to play a role in neuropsychiatric disorders. The probiotic bacterium Lactobacillus (L.) reuteri and products of tryptophan degradation, specifically the neuroactive kynurenine pathway (KP) metabolite kynurenic acid (KYNA), have received special attention in this context. We, therefore, assessed relevant features of KP metabolism, namely, the cellular uptake of the pivotal metabolite kynurenine and its conversion to its primary products KYNA, 3-hydroxykynurenine and anthranilic acid in L. reuteri by incubating the bacteria in Hank's Balanced Salt solution in vitro. Kynurenine readily entered the bacterial cells and was preferentially converted to KYNA, which was promptly released into the extracellular milieu. De novo production of KYNA increased linearly with increasing concentrations of kynurenine (up to 1 mM) and bacteria (10 ⁷ to 10 ⁹ CFU/mL) and with incubation time (1-3 h). KYNA neosynthesis was blocked by two selective inhibitors of mammalian kynurenine aminotransferase II (PF-048559989 and BFF-122). In contrast to mammals, however, kynurenine uptake was not influenced by other substrates of the mammalian large neutral amino acid transporter, and KYNA production was not affected by the presumed competitive enzyme substrates (glutamine and α-aminoadipate). Taken together, these results reveal substantive qualitative differences between bacterial and mammalian KP metabolism.

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P50 MH103222 United States MH NIMH NIH HHS; MH103222 United States MH NIMH NIH HHS

Keywords: cognition; gut–brain axis; kynurenine aminotransferases; kynurenine pathway; psychiatric disorders

343-65-7 (Kynurenine)
H030S2S85J (Kynurenic Acid)
0 (Amino Acids)

Date Created: 20240413 Date Completed: 20240415 Latest Revision: 20240425

20240425

PMC11011989

10.3390/ijms25073679

38612489