The Effect of Inulin‐Type Fructans on Plasma Trimethylamine N‐Oxide Levels in Peritoneal Dialysis Patients: A Randomized Crossover Trial

Abstract

Scope: Trimethylamine N-oxide (TMAO), an important proatherogenic uremic toxin, is oxidized by hepatic-flavin monooxygenases from gut microbiome-generated trimethylamine (TMA). The present study aims to explore whether manipulating the gut microbiota by inulin-type fructans (ITFs) can reduce circulating TMAO levels in peritoneal dialysis patients. Methods and results: This is a randomized, double-blind, placebo-controlled, crossover trial with 10 g day −1 ITFs intervention for 3 months in continuous ambulatory peritoneal dialysis patients. The gut microbiome is measured, and TMA-producing gene clusters are annotated using shotgun metagenomic sequencing. Fecal and plasma TMA, plasma TMAO, and daily urine excretion and dialysis removal of TMAO are measured. Finally, 22 participants complete the trial. The daily intake of macronutrients and TMAO precursors is comparable during the prebiotics, washout, and placebo interventions. The ITFs intervention increases the Firmicutes/Bacteroidetes (F/B) ratio (p = 0.049) of gut microbiome. However, no significant influences are observed on fecal TMA content, circulating TMAO levels, or TMA-producing gene clusters, including choline TMA-lyase (CutC/D), carnitine monooxygenase (CntA/B), and betaine reductase (GrdH). Conclusions: Intervention with 10 g day −1 of ITFs for 3 months is not sufficient to reduce plasma TMAO levels in peritoneal dialysis patients, but it improves the gut microbiome composition.

Immunomodulatory effects of inulin and its intestinal metabolites

“…However, in another study, intervention with inulin-type fructans (10 g/day) for 3 months altered composition of gut microbiome, but did not reduce the plasma TMAO level in patients undergoing peritoneal dialysis ( 130 ). This observation may be related to the duration and dose of the intervention.…”

Using the concept of food as medicine to mitigate inflammation in patients undergoing peritoneal dialysis

“…Moreover, a study using 21 g/day of unripe banana flowers for 4 weeks decreased the indoxyl sulfate (IS) in patients undergoing PD [93]. Although the previous studies demonstrate that the supplementation changed the gut microbiota and affected the plasma levels of some uremic toxins in PD, [94] demonstrated that 10 g/day of inulin was not sufficient to decrease the TMAO serum levels, another uremic toxin associated with inflammation and CVD in patients with CKD undergoing dialysis [94]. The use of prebiotic fiber needs more studies, but so far, promising results in mitigating factors related to inflammation have already been demonstrated.…”

Strategies for applying probiotics in the antibiotic management of Clostridioides difficile infection

“…143 Xiong et al found that ITFs increased the Firmicutes/Bacteroidetes (F/B) ratio and improved the gut microbial composition in peritoneal dialysis patients. 144 B. infant and human milk oligosaccharides (HMOs) comprised a synbiotic that increased the level of butyric acid in the adult gut and inhibited other harmful bacteria, thus maintaining the gut homeostasis. 65 Makki et al found that oligofructose increased the abundance of 6α-hydroxybile acid-associated bacteria and suggested that the pairing of oligofructose with 6α-hydroxybile acid-producing bacteria could be a new therapeutic option for patients with type II diabetes.…”