Paradox of trimethylamine-N-oxide, the impact of malnutrition on microbiota-derived metabolites and septic patients

Abstract

Background Trimethylamine N-oxide (TMAO) is a microbiota-derived metabolite, which is linked to vascular inflammation and atherosclerosis in cardiovascular (CV) diseases. But its effect in infectious diseases remains unclear. We conducted a single-center prospective study to investigate association of TMAO with in-hospital mortality in septic patients admitted to an intensive care unit (ICU). Methods Totally 95 septic, mechanically ventilated patients were enrolled. Blood samples were obtained within 24 h after ICU admission, and plasma TMAO concentrations were determined. Septic patients were grouped into tertiles according to TMAO concentration. The primary outcome was in-hospital death, which further classified as CV and non-CV death. Besides, we also compared the TMAO concentrations of septic patients with 129 non-septic patients who were admitted for elective coronary angiography (CAG). Results Septic patients had significantly lower plasma TMAO levels than did subjects admitted for CAG (1.0 vs. 3.0 μmol/L, p < 0.001). Septic patients in the lowest TMAO tertile (< 0.4 μmol/L) had poorer nutrition status and were given longer antibiotic courses before ICU admission. Circulating TMAO levels correlated positively with daily energy intake, the albumin and prealbumin concentration. Compared with those in the highest TMAO tertile, septic patients in the lowest TMAO tertile were at greater risk of non-CV death (hazard ratio 2.51, 95% confidence interval 1.21–5.24, p = 0.014). However, TMAO concentration was no longer an independent predictor for non-CV death after adjustment for disease severity and nutritional status. Conclusion Plasma TMAO concentration was inversely associated with non-CV death among extremely ill septic patients, which could be characterized as TMAO paradox. For septic patients, the impact of malnutrition reflected by circulating TMAO levels was greater than its pro-inflammatory nature.

Shotgun metagenomics and systemic targeted metabolomics highlight indole-3-propionic acid as a protective gut microbial metabolite against influenza infection

“…The level of TMAO was low on D7, likely due to low food intake. 59 In contrast, the TMAO levels were significantly elevated on D14. Given that the serum TMAO concentration is associated with many diseases ranging from inflammatory diseases (e.g., pneumonia) to metabolic and cardiovascular diseases, 28 , 60 one can reasonably expect an elevated TMAO level can have negative consequences in IAV-infected hosts.…”

Atherosclerosis and trimethylamine-N-oxide — the gut microbiota potential

“…Уровень ТМАО в плазме не был связан с классическими сердечнососудистыми факторами риска и с эндотелиальной функцией в здоровой когорте [30]. Концентрация ТМАО в плазме обратно пропорциональна смертности среди тяжелобольных септических пациентов без ССЗ, что можно охарактеризовать как парадокс ТМАО [40]. Положительные эффекты ТМАО зависят от контекста, например, в условиях стресса в моделях переедания ТМАО может проявлять антиоксидантные и противовоспалительные эффекты, наблюдаемые на тканевом уровне, особенно в гепатоцитах, адипоцитах, мышечной ткани и β-клетках поджелудочной железы, а также влияние ТМАО на толерантность к глюкозе различается между здоровыми условиями и патогенными состояниями [28].…”

The Intestinal Flora Metabolite Trimethylamine Oxide Is Inextricably Linked to Coronary Heart Disease

“… 80 Another investigation examining 95 patients with sepsis revealed that the impact of malnutrition reflected by plasma TMAO levels in these patients was far more significant than TMAO's proinflammatory effects. 84 Taken together, reducing choline intake rather than eliminating it is beneficial to patients with cardiovascular disease to some extent.…”