Actions of Trace Amines in the Brain-Gut-Microbiome Axis via Trace Amine-Associated Receptor-1 (TAAR1)

Gwilt, Katlynn Bugda; González, Dulce Pamela; Olliffe, Neva; Oller, Haley; Hoffing, Rachel; Puzan, Marissa; Aidy, Sahar El; Miller, Gregory M.

doi:10.1007/s10571-019-00772-7

Cited by 37 publications

(22 citation statements)

References 118 publications

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“…It has been shown that gut bacteria produce the neurotransmitter tyramine 49 . The highly increased level of its metabolite, tyramine-O-sulfate, in fecal samples of mice consuming HCl-acidified drinking water indicates altered tyramine synthesis and metabolism, which can affect gastrointestinal physiology and neurological function 50 .…”

Section: Discussionmentioning

confidence: 99%

The acidified drinking water-induced changes in the behavior and gut microbiota of wild-type mice depend on the acidification mode

Whipple

Agar

Zhao

et al. 2021

Sci Rep

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Acidification of drinking water to a pH between 2.5 and 3.0 is widely used to prevent the spread of bacterial diseases in animal colonies. Besides hydrochloric acid (HCl), sulfuric acid (H2SO4) is also used to acidify drinking water. Here we examined the effects of H2SO4-acidified drinking water (pH = 2.8) received from weaning (postnatal day 21) on the behavior and gut microflora of 129S6/SvEv mice, a mouse strain commonly used in transgenic studies. In contrast to HCl-acidified water, H2SO4-acidified water only temporarily impaired the pole-descending ability of mice (at 3 months of age), and did not change the performance in an accelerating rotarod test. As compared to 129S6/SvEv mice receiving non-acidified or HCl-acidified drinking water, the gut microbiota of 129S6/SvEv mice on H2SO4-acidified water displayed significant alterations at every taxonomic level especially at 6 months of age. Our results demonstrate that the effects of acidified drinking water on the behavior and gut microbiota of 129S6/SvEv mice depends on the acid used for acidification. To shed some light on how acidified drinking water affects the physiology of 129S6/SvEv mice, we analyzed the serum and fecal metabolomes and found remarkable, acidified water-induced alterations.

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Section: Discussionmentioning

confidence: 99%

The acidified drinking water-induced changes in the behavior and gut microbiota of wild-type mice depend on the acidification mode

Whipple

Agar

Zhao

et al. 2021

Sci Rep

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“…Microbes are powerful in catabolizing AAs into a great variety of derivatives [ 39 , 40 ], many of which, including amines, nitric oxide (NO), indole, kynurenine, and quinolone, are neurologically active or affect human behavior through actions on the immune or endocrine system [ 41 , 42 ]. Key enzymes of AA-catabolism fall into three categories that participate in the decarboxylation, transamination, and deamination of AAs, respectively.…”

Section: Resultsmentioning

confidence: 99%

Enhanced intestinal protein fermentation in schizophrenia

Liang

Shi

Shen

et al. 2022

BMC Med

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Background Emerging findings highlighted the associations of mental illness to nutrition and dysbiosis in the intestinal microbiota, but the underlying mechanisms, especially in schizophrenia (SZ), remain unclarified. Methods We conducted a case-control study of SZ patients (case to control=100:52) by performing sequencing of the gut metagenome; measurement of fecal and plasma non-targeted metabolome; including short-, medium-, and long-chain fatty acids; and targeted metabolites, along with recorded details of daily intakes of food. Results The metagenome analysis uncovered enrichment of asaccharolytic species and reduced abundance of carbohydrate catabolism pathways and enzymes in the gut of SZ patients, but increased abundance of peptidases in contrast to their significantly reduced protein intake. Fecal metabolome analysis identified increased concentrations of many protein catabolism products, including amino acids (AAs), urea, branched short-chain fatty acids, and various nitrogenous derivates of aromatic AAs in SZ patients. Protein synthesis, represented by the abundance of AA-biosynthesis pathways and aminoacyl-tRNA transferases in metagenome, was significantly decreased. The AUCs (area under the curve) of the diagnostic random forest models based on their abundance achieved 85% and 91%, respectively. The fecal levels of AA-fermentative enzymes and products uniformly showed positive correlations with the severity of psychiatric symptoms. Conclusions Our findings revealed apparent dysbiosis in the intestinal microbiome of SZ patients, where microbial metabolism is dominated by protein fermentation and shift from carbohydrate fermentation and protein synthesis in healthy conditions. The aberrant macronutrient metabolism by gut microbes highlights the importance of nutrition care and the potential for developing microbiota-targeted therapeutics in SZ.

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“…Furthermore, we examined if Klamin ® induced relaxant effects via a direct action on the smooth muscle cells and/or via an indirect action involving neural pathways. Indeed, mouse and human studies reported that TAAR1 receptors are located in intestinal epithelial cells as well as enteric neurons of both submucosa and myenteric plexus [22,49,50].…”

Section: Discussionmentioning

confidence: 99%

Spasmolytic Effects of Aphanizomenon Flos Aquae (AFA) Extract on the Human Colon Contractility

et al. 2021

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The blue-green algae Aphanizomenon flos aquae (AFA), rich in beneficial nutrients, exerts various beneficial effects, acting in different organs including the gut. Klamin® is an AFA extract particularly rich in β-PEA, a trace-amine considered a neuromodulator in the central nervous system. To date, it is not clear if β-PEA exerts a role in the enteric nervous system. The aims of the present study were to investigate the effects induced by Klamin® on the human distal colon mechanical activity, to analyze the mechanism of action, and to verify a β-PEA involvement. The organ bath technique, RT-PCR, and immunohistochemistry (IHC) were used. Klamin® reduced, in a concentration-dependent manner, the amplitude of the spontaneous contractions. EPPTB, a trace-amine receptor (TAAR1) antagonist, significantly antagonized the inhibitory effects of both Klamin® and exogenous β-PEA, suggesting a trace-amine involvement in the Klamin® effects. Accordingly, AphaMax®, an AFA extract containing lesser amount of β-PEA, failed to modify colon contractility. Moreover, the Klamin® effects were abolished by tetrodotoxin, a neural blocker, but not by L-NAME, a nitric oxide-synthase inhibitor. On the contrary methysergide, a serotonin receptor antagonist, significantly antagonized the Klamin® effects, as well as the contractility reduction induced by 5-HT. The RT-PCR analysis revealed TAAR1 gene expression in the colon and the IHC experiments showed that 5-HT-positive neurons are co-expressed with TAAR1 positive neurons. In conclusion, the results of this study suggest that Klamin® exerts spasmolytic effects in human colon contractility through β-PEA, that, by activating neural TAAR1, induce serotonin release from serotoninergic neurons of the myenteric plexus.

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Actions of Trace Amines in the Brain-Gut-Microbiome Axis via Trace Amine-Associated Receptor-1 (TAAR1)

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Cited by 37 publications

References 118 publications

The acidified drinking water-induced changes in the behavior and gut microbiota of wild-type mice depend on the acidification mode

The acidified drinking water-induced changes in the behavior and gut microbiota of wild-type mice depend on the acidification mode

Enhanced intestinal protein fermentation in schizophrenia

Spasmolytic Effects of Aphanizomenon Flos Aquae (AFA) Extract on the Human Colon Contractility

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