Alterations to microbial secretome by estrogen may contribute to sex bias in irritable bowel syndrome.

INTRODUCTION: Irritable bowel syndrome (IBS) is a female predominant functional gastrointestinal disorder, underpinned by microbial dysbiosis and microinflammation. We suggest that changes in trace amine (TA) load and metabolism may link together diet, inflammation and sex in this context. METHODS: The effect of E2 treatment on microbial growth and TA generation was assessed using liquid chromatography and tandem mass spectrometry methodology. To investigate the effects of TAs on the gut, WST-1, prostaglandin E2 and tight junction protein dynamics were investigated in TA treated (HT-29) colon epithelial monolayer cultures. RESULTS: Differential E2-dependent alterations of the TA production capabilities of microbes were observed. Significantly, E2 treatment resulted in a 50% increase in tryptamine secretion from a probiotic microbe (p < 0.0001). Moreover, in vitro experiments indicated that TA treatment exerted type-specific effects in the gut, e.g., reducing mitochondrial functionality, even at low doses of tryptamine (p < 0.0001) and ρ-tyramine (p < 0.001). Additionally, prostaglandin E2 levels were significantly increased following ρ-tyramine and agmatine treatment (p < 0.05). In terms of functionality, all investigated TAs resulted in occludin redistribution and loss of zona occludens-1 and occludin co-localization. CONCLUSION: Increases in the gastrointestinal TA load may contribute to a relatively pro-inflammatory outcome in the intestine, along with tight junction protein disruption. Additionally, fluctuating levels of endogenous E2 may modulate microbially-derived TA levels, potentially explaining exaggerating gastrointestinal symptomology in females during low E2 phases. Thus, current data warrants subsequent investigations in appropriate in vivo models to fully elucidate the role of the trace aminergic system in the sex bias observed in IBS.

Effect of Chronic Dolutegravir Administration on the Trace Amine Profile in Wistar Rats.

BACKGROUND: Dolutegravir (DTG), an integrase strand inhibitor, is currently used as the first-line treatment for HIV. Despite relatively poor tissue penetration, the risk of adverse effects in metabolic and excretory systems should be considered. The trace aminergic system and trace amines are emerging as relevant role players in many chronic diseases that are commonly diagnosed but poorly understood. Trace amines are biogenic amines that are endogenously produced and can also be ingested by the intake of trace amine-rich food. Trace amines are known to differentially regulate inflammatory and neurological outcome. OBJECTIVE: This study investigated the effects of DTG on the trace amine profile in a wistar rat model. METHODS: A total of 24 healthy wistar rats were randomly divided into four experimental groups: male and female controls and male and female DTG-treated. Blood and tissue samples were collected following a 12-week DTG administration study. Liquid chromatography-tandem mass spectroscopy (LC-MS/MS) was used to determine trace amine concentrations in urine, plasma, brain, and gastrointestinal tissue. RESULTS: Current data illustrate that polyamines differ significantly (p < 0.05) between males and females in various matrices. DTG significantly (p < 0.05) reduced jejunal tyramine and urinary synephrine levels. CONCLUSION: Data do not raise major concerns about DTG in the context of the trace amine profile. However, given the importance of the dysregulated trace amine profile in various diseased states, including HIV, current data warrant clinical investigation to further evaluate the significance of DTG-associated effects on the trace amine profile.