Gut Microbial Metabolites and Blood Pressure Regulation: Focus on SCFAs and TMAO

Poll, Brian G.; Cheema, Muhammad Umar; Pluznick, Jennifer L.

doi:10.1152/physiol.00004.2020

Cited by 57 publications

(48 citation statements)

References 116 publications

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“…Those findings were in line with the results from this cohort study. Of further note, experimental studies have provided evidence about the importance and causal role of TMAO in cardiovascular disease [ 11 ]. It has been proposed that the role of TMAO in the risk of cardiovascular disease could be mediated by several pathways, such as the acceleration of atherosclerosis by enhancing the formation of foam cells and atherosclerotic plaques [ 1 ], the inhibition of reverse cholesterol process whereby cholesterol is transported form the arterial wall back to the liver where it is metabolized and excreted in the bile [ 2 ], as well as the platelet hyperactivity, nevertheless the entire mechanisms are not fully understood [ 32 ].…”

Section: Discussionmentioning

confidence: 99%

“…The role of gut microbiota-derived metabolites in the development of cardiovascular disease has gained recent attention [ 11 ], particularly in individuals with T2D [ 34 ]. Nevertheless, the association of TMAO with risk of cardiovascular mortality in subjects with T2D has not being sufficiently studied.…”

Section: Discussionmentioning

confidence: 99%

“…Trimethylamine (TMA) is a by-product of a microbial fermentation, in which the gut microbiota metabolizes dietary components such as phosphatidylcholine, choline, and L-carnitine to be used as carbon fuel supply by the gut microbiota. Subsequently, the conversion of TMA to TMAO occurs in the host liver by the flavin monooxygenase 3, after which it is cleared by the kidneys [ 11 ].…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Circulating Trimethylamine N-Oxide Is Associated with Increased Risk of Cardiovascular Mortality in Type-2 Diabetes: Results from a Dutch Diabetes Cohort (ZODIAC-59)

Flores‐Guerrero

Dijk

Connelly

et al. 2021

JCM

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Trimethylamine N-oxide (TMAO), a novel cardiovascular (CV) disease and mortality risk marker, is a gut microbiota-derived metabolite as well. Recently, plasma concentrations of branched-chain amino acids (BCAA) have been reported to be affected by microbiota. The association of plasma TMAO with CV mortality in Type 2 Diabetes (T2D) and its determinants are still incompletely described. We evaluated the association between plasma BCAA and TMAO, and the association of TMAO with CV mortality in T2D individuals. We used data of 595 participants (mean age 69.5 years) from the Zwolle Outpatient Diabetes project Integrating Available Care (ZODIAC) cohort were analyzed. Plasma TMAO and BCAA were measured with nuclear magnetic resonance spectroscopy. CV mortality risk was estimated using multivariable-adjusted Cox regression models. Cross-sectionally, TMAO was independently associated with BCAA standardized (Std) β = 0.18 (95% Confidence Interval (CI) 0.09; 0.27), p <0.001. During a median follow-up of 10 years, 113 CV deaths were recorded. In Cox regression analyses, adjusted for multiple clinical and laboratory variables including BCAA, TMAO was independently associated with CV mortality: adjusted hazard ratio (adjHR) 1.93 (95% CI 1.11; 3.34), p = 0.02 (for the highest vs. the lowest tertile of the TMAO distribution). The same was true for analyses with TMAO as continuous variable: adjHR 1.32 (95% CI 1.07; 1.63), p = 0.01 (per 1 SD increase). In contrast, BCAAs were not associated with increased CV mortality. In conclusion, higher plasma TMAO but not BCAA concentrations are associated with an increased risk of CV mortality in individuals with T2D, independent of clinical and biochemical risk markers.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Circulating Trimethylamine N-Oxide Is Associated with Increased Risk of Cardiovascular Mortality in Type-2 Diabetes: Results from a Dutch Diabetes Cohort (ZODIAC-59)

Flores‐Guerrero

Dijk

Connelly

et al. 2021

JCM

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“…An additional advantage of Acetated Ringer's solution is that the rate of acetate metabolism to bicarbonate is faster than that of L-lactate ( 39 , 41 , 70 ). The main disadvantage of acetated Ringer's solution is that the solution is vasodilatory due to the inclusion of acetate ( 74 – 76 ), resulting in mild decreases in mean arterial blood pressure during infusion. This reduction may be clinically important in critically ill neonatal calves.…”

Section: Intravenous Fluid Therapy In Neonatal Calves With Diarrheamentioning

confidence: 99%

Intravenous and Oral Fluid Therapy in Neonatal Calves With Diarrhea or Sepsis and in Adult Cattle

et al. 2021

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Optimal fluid therapy protocols in neonatal calves and adult cattle are based on consideration of signalment, history, and physical examination findings, and individually tailored whenever laboratory analysis is available. Measurement of the magnitude of eye recession, duration of skin tenting in the lateral neck region, and urine specific gravity by refractometry provide the best estimates of hydration status in calves and cattle. Intravenous and oral electrolyte solutions (OES) are frequently administered to critically ill calves and adult cattle. Application of physicochemical principles indicates that 0.9% NaCl, Ringer's solution, and 5% dextrose are equally acidifying, lactated Ringer's and acetated Ringer's solution are neutral to mildly acidifying, and 1.3–1.4% sodium bicarbonate solutions are strongly alkalinizing in cattle. Four different crystalloid solutions are recommended for intravenous fluid therapy in dehydrated or septic calves and dehydrated adult cattle: (1) lactated Ringer's solution and acetated Ringer's solution for dehydrated calves, although neither solution is optimized for administration to neonatal calves or adult cattle; (2) isotonic (1.3%) or hypertonic (5.0 or 8.4%) solutions of sodium bicarbonate for the treatment of calves with diarrhea and severe strong ion (metabolic) acidosis and hyponatremia, and adult cattle with acute ruminal acidosis; (3) Ringer's solution for the treatment of metabolic alkalosis in dehydrated adult cattle, particularly lactating dairy cattle; and (4) hypertonic NaCl solutions (7.2%) and an oral electrolyte solution or water load for the rapid resuscitation of dehydrated neonatal calves and adult cattle. Much progress has been made since the 1970's in identifying important attributes of an OES for diarrheic calves. Important components of an OES for neonatal calves are osmolality, sodium concentration, the effective SID that reflects the concentration of alkalinizing agents, and the energy content. The last three factors are intimately tied to the OES osmolality and the abomasal emptying rate, and therefore the rate of sodium delivery to the small intestine and ultimately the rate of resuscitation. An important need in fluid and electrolyte therapy for adult ruminants is formulation of a practical, effective, and inexpensive OES.

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“…In addition, the relative abundance of SCFA-producing Dialister, Megasphaera, Turicibacter , and Sharpea were increased in the MET group, which may also explain the increased production of SCFAs in the intestine. As the main source of energy for epithelial cells, SCFA can increase the proliferation of intestinal tissues ( 48 , 49 ), butyrate can decrease intestinal inflammation, and as it enhances the intestinal barrier function ( 50 ), propionate can be used by hepatocyte cells of the liver for gluconeogenesis ( 51 ). That beneficial bacteria were increased in the MET offspring may be associated with the increase of SCFAs, which destroy microbial pathogens ( 52 ).…”

Section: Discussionmentioning

confidence: 99%

Methyl-Donor Micronutrient for Gestating Sows: Effects on Gut Microbiota and Metabolome in Offspring Piglets

Zou

et al. 2021

Front. Nutr.

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This study aimed to investigate the effects of maternal methyl-donor micronutrient supplementation during gestation on gut microbiota and the fecal metabolic profile in offspring piglets. Forty-three Duroc × Erhualian gilts were assigned to two dietary groups during gestation: control diet (CON) and CON diet supplemented with MET (folic acid, methionine, choline, vitamin B6, and vitamin B12). The body weights of offspring piglets were recorded at birth and weaning. Besides this, fresh fecal samples of offspring piglets were collected at 7, 14, and 21 days. The gut microbiota composition, metabolic profile, and short-chain fatty acid (SCFA) profiles in the fecal samples were determined using 16S rDNA sequencing, liquid chromatography-mass spectrometry metabolomics, and gas chromatography methods, respectively. The results showed that maternal methyl-donor micronutrient supplementation increased the microbiota diversity and uniformity in feces of offspring piglets as indicated by increased Shannon and Simpson indices at 7 days, and greater Simpson, ACE, Chao1 and observed species indices at 21 days. Specifically, at the phylum level, the relative abundance of Firmicutes and the Firmicutes to Bacteroidetes ratio were elevated by maternal treatment. At the genus level, the relative abundance of SCFA-producing Dialister, Megasphaera, and Turicibacter, and lactate-producing Sharpea as well as Akkermansia, Weissella, and Pediococcus were increased in the MET group. The metabolic analyses show that maternal methyl-donor micronutrient addition increased the concentrations of individual and total SCFAs of 21-day piglets and increased metabolism mainly involving amino acids, pyrimidine, and purine biosynthesis. Collectively, maternal methyl-donor micronutrient addition altered gut microbiota and the fecal metabolic profile, resulting in an improved weaning weight of offspring piglets.

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Gut Microbial Metabolites and Blood Pressure Regulation: Focus on SCFAs and TMAO

Cited by 57 publications

References 116 publications

Circulating Trimethylamine N-Oxide Is Associated with Increased Risk of Cardiovascular Mortality in Type-2 Diabetes: Results from a Dutch Diabetes Cohort (ZODIAC-59)

Circulating Trimethylamine N-Oxide Is Associated with Increased Risk of Cardiovascular Mortality in Type-2 Diabetes: Results from a Dutch Diabetes Cohort (ZODIAC-59)

Intravenous and Oral Fluid Therapy in Neonatal Calves With Diarrhea or Sepsis and in Adult Cattle

Methyl-Donor Micronutrient for Gestating Sows: Effects on Gut Microbiota and Metabolome in Offspring Piglets

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