<p>Trimethylamine N-Oxide, a Gut Microbiota-Dependent Metabolite, is Associated with Frailty in Older Adults with Cardiovascular Disease</p>

Abstract

Objective: Our study aimed to explore the association between trimethylamine N-oxide and frailty in older adults with cardiovascular disease. Patients and Methods: This cross-sectional study analyzed a total of 451 people aged 65 years or older who underwent comprehensive geriatric assessments. Frailty status was determined using a frailty index constructed with 48 variables according to the cumulative deficits model. Physical frailty and cognitive frailty were also assessed in detail. Fasting plasma TMAO was measured by mass spectrometry. Results: The proportion of frail subjects was 29.9% (135/451). Plasma TMAO levels were significantly higher in frail patients than in nonfrail individuals (4.04 [2.84-7.01] vs 3.21 [2.13-5.03] µM; p<0.001). Elevated plasma TMAO levels were independently associated with the likelihood of frailty (OR 2.12, 95% CI 1.01-4.38, p=0.046). Dose-response analysis revealed a linear association between the TMAO concentration and the OR for frailty. A 2-unit increase in TMAO was independently correlated with physical frailty (OR 1.23, 95% CI 1.08-1.41, p for trend 0.002) and cognitive frailty (OR 1.21, 95% CI 1.01-1.45, p for trend 0.04). Conclusion: Elevated circulating TMAO levels are independently associated with frailty among older adults with cardiovascular disease.

Regulation of blood–brain barrier integrity by microbiome-associated methylamines and cognition by trimethylamine N-oxide

“…Numerous groups have investigated the putative relationship between TMAO and cognition following reports of an association between cerebrospinal fluid TMAO content and Alzheimer’s disease [ 28 ], with negative correlations between plasma TMAO content and cognitive function having been identified in both clinical [ 66 , 72 , 73 ] and experimental [ 29 , 68 , 69 ] settings. Whether this relationship is truly deterministic remains unclear, however, as the role of the immediate precursor to TMAO—TMA—in cognition and vascular function has largely been overlooked.…”

Trimethylamine N-oxide (TMAO) in human health

“…Researchers pay a lot of attention to the intestinal microbiome because of its possible role as a promoter of chronic diseases, cancers and even neurological disorders (Janeiro et al, 2018[ 28 ]). Intestinal microflora is connected with new age disorders like obesity (Musso et al, 2010[ 52 ]), insulin resistance (Musso et al, 2010[ 52 ]; Diamant et al, 2011[ 15 ]; Miele et al, 2015[ 44 ]; Tai et al, 2015[ 69 ]), atherosclerosis (Dalla Via et al, 2020[ 13 ]), cardiovascular diseases (ischemic stroke) (He et al, 2020[ 26 ]; Schneider et al, 2020[ 63 ]), as well as type 2 diabetes (Tai et al, 2015[ 69 ]), kidney failure (Bain et al, 2006[ 4 ]; Tang et al, 2015[ 70 ]; Missailidis et al, 2016[ 47 ]; Stubbs et al, 2016[ 66 ]; Mafune et al, 2016[ 41 ]), neurological disorders (Cryan and Dinan, 2012[ 12 ]), and cancer (stomach, colon) (Erdman and Poutahidis, 2015[ 18 ]; Dey and Ciorba, 2016[ 14 ]; Wang et al, 2019[ 79 ]). TMAO was also associated with mortality and hospitalization for cardiorenal disorders, including atrial fibrillation (Tang et al, 2014[ 71 ]), heart failure (Trøseid et al, 2015[ 73 ]), acute myocardial infarction (Suzuki et al, 2017[ 68 ]), and chronic kidney disease (Tang et al, 2015[ 70 ]).…”

“…In research conducted by He et al (2020[ 26 ]) 451 people aged 65 or older took part. The aim of this study was to identify the relationship between the levels of plasma TMAO and frailty in older people with cardiovascular disease (CVD) using UPLC-MS/MS.…”

“…They found that in frail participants the levels of TMAO were significantly higher compared to non-frail participants, 4.04 µM vs. 3.21 µM, respectively. Researchers suggested that elevated levels of TMAO are independently associated with frailty among older adults with CVD (He et al, 2020[ 26 ]). As it is well known the levels of TMAO correlate with the risk of CVD, but some conflicting data suggested a specific role of this compound in ischemic stroke.…”

Regulation of blood–brain barrier integrity by microbiome-associated methylamines and cognition by trimethylamineN-oxide

“…Numerous groups have investigated the putative relationship between TMAO and cognition following reports of an association between cerebrospinal fluid TMAO content and Alzheimer's disease 28 , with negative correlations between plasma TMAO content and cognitive function having been identified in both clinical [65][66][67] and experimental 29,68,69 settings. Whether this relationship is truly deterministic remains unclear, however, as the role of the immediate precursor to TMAO, TMA, in cognition and vascular function has largely been overlooked.…”