Impaired intestinal function is associated with lower muscle and cognitive health and well‐being in patients with congestive heart failure

Abstract

Background Small‐ and large‐intestinal perturbations have been described as prevalent extracardiac systemic manifestations in congestive heart failure (CHF), but alterations in protein digestion and absorption and plasma short‐chain fatty acid (SCFA) concentrations and the potential link with other systemic effects (muscle and cognitive health) have not been investigated in CHF. Methods We analyzed protein digestion and absorption with dual stable tracer method in 14 clinically stable, noncachectic CHF outpatients (mean left ventricular ejection fraction: 35.5% [95% CI, 30.9%–40.1%]) and 15 controls. Small‐intestinal non–carrier‐mediated permeability and active carrier‐mediated glucose transport were quantified by sugar permeability test. Plasma SCFA (acetate, propionate, butyrate, isovalerate, valerate) concentrations were measured as intestinal microbial metabolites. Muscle function was assessed by isokinetic dynamometry, cognition by a battery of tests, and well‐being by questionnaire. Results Protein digestion and absorption were impaired by 29.2% (P = .001) and active glucose transport by 38.4% (P = .010) in CHF. Non–carrier‐mediated permeability was not altered. Whereas plasma propionate, butyrate, and isovalerate concentrations were lower in CHF (P < .05), acetate and valerate concentrations did not differ. Overall, intestinal dysfunction was associated with impaired leg muscle quality, emotional distress, and cognitive dysfunction (P < .05). Conclusions We identified impaired protein digestion and absorption and altered SCFA concentrations as additional intestinal dysfunctions in CHF that are linked to reduced muscle and cognitive health and well‐being. More research is needed to implement strategies to improve intestinal function in CHF and to investigate the mechanisms underlying its link with other systemic manifestations.

Intestinal dysfunction in chronic disease

“…the combined oral intake of an intrinsically labeled protein with a differently labeled free dietary amino acid, can be used to analyze intestinal protein digestion and absorption [16]. After a bolus meal ingestion [6 ▪ ,13,29], blood or urine should be collected over several hours while with sip feeding [25 ▪ ,26], one sample can be taken at a time point when there is steady state of intake and digestion and absorption. Usually, this is after 2 h of sip feeding with a protein hydrolysate [25 ▪ ,26,27].…”

“…Increased intestinal permeability or loss of intestinal barrier function have been described in many chronic diseases, such as CHF [35], COPD [13], cancer [7], liver cirrhosis [9] and chronic kidney diseases [10], but results are not always congruent [6 ▪ ,29], possibly due to differences in the used methods and study populations. A subsequent uncontrolled translocation of endotoxins can potentially evoke systemic inflammation [7] and deteriorate the underlying chronic disease and worsen overall well-being and functioning.…”

Mechanisms shared between cancer, heart failure, and targeted anti-cancer therapies

“…216 Plasma SCFA levels are decreased in patients with HF. 217 and SCFA supplementation attenuates HF in mice. [218][219][220] Butyrate supplementation protected from doxorubicin induced cardiotoxicity in vivo.…”

Circulating metabolic signatures of heart failure in precision cardiology

“… 55 , 56 In a study of 14 CHF outpatients, propionate, butyrate, and isovalerate concentrations were lower in CHF patients, while acetate and valerate concentrations did not differ. 57 A recent study has proven that butyrate, as an alternative for impaired LCFA oxidation, was the preferred energy source over ketone bodies in HF. The enhanced butyrate oxidation in HF was associated with an increase in synthetase medium chain family member (ACSM) 3, a mitochondrial enzyme activating butyrate to butyryl CoA.…”