D-Pipecolinic acid

Depression and anxiety in patients with active ulcerative colitis: crosstalk of gut microbiota, metabolomics and proteomics

Patients with ulcerative colitis (UC) have a high prevalence of mental disorders, such as depression and anxiety. Gut microbiota imbalance and disturbed metabolism have been suggested to play an important role in either UC or mental disorders. However, little is known about their detailed multi-omics characteristics in patients with UC and depression/anxiety. In this prospective observational study, 240 Chinese patients were enrolled, including 129 patients with active UC (69 in Phase 1 and 60 in Phase 2; divided into depression/non-depression or anxiety/non-anxiety groups), 49 patients with depression and anxiety (non-UC), and 62 healthy people. The gut microbiota of all subjects was analyzed using 16S rRNA sequencing. The serum metabolome and proteome of patients with UC in Phase 2 were analyzed using liquid chromatography/mass spectrometry. Associations between multi-omics were evaluated by correlation analysis. The prophylactic effect of candidate metabolites on the depressive-like behavior of mice with colitis was investigated. In total, 58% of patients with active UC had depression, while 50% had anxiety. Compared to patients with UC without depression/anxiety, patients with UC and depression/anxiety had lower fecal microbial community richness and diversity, with more Lactobacillales, Sellimonas, Streptococcus, and Enterococcus but less Prevotella_9 and Lachnospira. Most metabolites (e.g., glycochenodeoxycholate) were increased in the serum, while few metabolites, including 2'-deoxy-D-ribose and L-pipecolic acid, were decreased, accompanied by a general reduction in immunoglobulin proteins. These related bacteria, metabolites, and proteins were highly connected. A prophylactic administration of 2'-deoxy-D-ribose and L-pipecolic acid significantly reduced the depressive-like behaviors in mice with colitis and alleviated the inflammatory cytokine levels in their colon, blood and brain. This study has identified a comprehensive multi-omics network related to depression and anxiety in active UC. It is composed of a certain set of gut microbiota, metabolites, and proteins, which are potential targets for clinical intervention for patients with UC and depression/anxiety.

Significance of the natural occurrence of L- versus D-pipecolic acid: a review

Pipecolic acid naturally occurs in microorganisms, plants, and animals, where it plays many roles, including the interactions between these organisms, and is a key constituent of many natural and synthetic bioactive molecules. This article provides a review of current knowledge on the natural occurrence of pipecolic acid and the known and potential significance of its L- and D-enantiomers in different scientific disciplines. Knowledge gaps with perspectives for future research identified within this article include the roles of the L- versus the D-enantiomer of pipecolic acid in plant resistance, nutrient acquisition, and decontamination of polluted soils, as well as rhizosphere ecology and medical issues.

The metabolism of D- and L-pipecolic acid in the rabbit and rat

The metabolism of D- and L-pipecolic acid has been investigated in rabbits and rats. A rapid evolution of 14CO2 followed the injection of either D- or L-pipe[6-14C]colic acid into rabbits. Rabbit kidney slices degraded to CO2 both isomers of lysine and of pipecolic acid. Rabbit liver was effective with only the L-isomers. In the rat, very little of injected L-pipecolic acid was catabolized to CO2, and large amounts were excreted unchanged into the urine, L-Lysine was efficiently metabolized to CO2 by rat liver and kidney slices but not D-lysine or either isomer of pipecolic acid. Rat kidney converted D-lysine to L-pipecolic acid. The L-isomer was identified by co-precipitation of the radioactive product with authentic compounds.

Determination of D- and L-pipecolic acid in food samples including processed foods

Background: Pipecolic acid, a metabolite of lysine, is found in human physiological fluids and is thought to play an important role in the central inhibitory gamma-aminobutyric acid system. However, it is unclear whether plasma D- and L-pipecolic acid originate from oral food intake or intestinal bacterial metabolites.
Methods: We analyzed the contents of D- and L-pipecolic acid in several processed foods including dairy products (cow's milk, cheese and yogurt), fermented beverages (beer and wine) and heated samples (beef, bovine liver, bread and tofu) to clarify the relationship between plasma D- and L-pipecolic acid and dietary foods.
Results: Our study revealed that some of the samples contained high concentrations of total pipecolic acid, and a higher proportion of L- than D-isomers. The other samples also showed high proportions of L-pipecolic acid. It was also shown that there is no significant change in the ratio of the D-isomer before and after heat treatment. The heat treatments could not cause the racemization of pipecolic acid in this study.
Conclusion: These findings suggest that plasma pipecolic acid, particularly the D-isomer, does not originate from direct food intake and that D- and L-pipecolic acid can possibly be derived from intestinal bacterial metabolites.

Plasma levels of pipecolic acid, both L- and D-enantiomers, in patients with chronic liver diseases, especially hepatic encephalopathy

Pipecolic acid is regarded as a gamma-aminobutyric acid receptor agonist. Stereochemical studies of pipecolic acid were performed in patients with chronic liver diseases. Plasma D- and L-pipecolic acid were significantly elevated in 15 liver cirrhotic patients with no history of hepatic encephalopathy (1.05+/-0.24 micromol/l, 1.58+/-0.13 micromol/l, p < 0.01) and in 27 patients with chronic hepatic encephalopathy (1.58+/-0.50 micromol/l, 2.38+/-0.58 micromol/l, p<0.001) compared to 15 normal subjects. In seven patients with chronic hepatic encephalopathy orally treated with kanamycin, plasma pipecolic acid significantly decreased (D-acid: before 1.62+/-0.23 micromol/l, after 0.61+/-0.15 micromol/l; p<0.01, L-acid: before 2.43-0.52 micromol/l, after 2.23+/-0.11 micromol/l; p< 0.05). These results suggest that plasma pipecolic acid, particularly D-acid, is produced from D-lysine by intestinal bacteria in liver cirrhotic patients and that pipecolic acid could be involved in the pathogenesis of hepatic encephalopathy.