# Fecal short-chain fatty acids and serum metabolites: the impact of COVID-19 infection on dialysis patients

## TL;DR

This study finds that dialysis patients with COVID-19 have reduced fecal short-chain fatty acids and altered serum metabolites, which may contribute to long-term complications.

## Contribution

The study identifies specific metabolic changes in dialysis patients with COVID-19 and links them to long-term outcomes.

## Key findings

- Infected dialysis patients had lower fecal short-chain fatty acids like propionate and butyrate.
- Serum metabolites related to amino acid and energy metabolism were altered in infected patients.
- Persistent amino-acid-centered metabolic changes were observed in patients who developed long COVID.

## Abstract

Patients undergoing dialysis are particularly susceptible to severe COVID-19 outcomes owing to pre-existing metabolic and immunological dysregulation, which may exacerbate clinical severity and elevate the risk of long COVID (LC). Nevertheless, the precise metabolic pathways implicated remain poorly characterized. This study aimed to characterize fecal short-chain fatty acids (SCFAs) and serum metabolomic signatures in dialysis patients with acute COVID-19 and to explore their association with LC.

Targeted liquid chromatography–tandem mass spectrometry (LC–MS/MS) quantified fecal SCFAs in 27 infected patients and 28 non-infected controls, and untargeted gas chromatography–mass spectrometry (GC–MS)-based metabolomics profiled serum samples from 23 infected patients and all 40 controls in partially overlapping patient subsets, with repeat serum sampling at 3 months and stratification into LC and non-LC groups. Multivariate analyses, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment, and Pearson correlation analyses between differential metabolites and routine clinical indicators were performed.

Infected patients exhibited significantly lower fecal levels of six SCFAs, including propionate and butyrate, compared with controls. Serum metabolomics identified 54 infection-related differential metabolites enriched in amino acid, energy, carbohydrate, and nucleotide metabolism, and 77 LC-associated metabolites predominantly mapping to amino acid and energy pathways. Pearson correlation analysis showed that amino acids and energy-supporting metabolites (e.g., glutamine, aspartate, methionine, cystine, taurine) were inversely correlated with C-reactive protein, leukocyte and neutrophil counts, and aspartate aminotransferase, but positively correlated with albumin, serum potassium, and lymphocyte or eosinophil counts, whereas purine degradation products and organic acids (e.g., uric acid, hypoxanthine, pyruvate, glycolate) exhibited the opposite pattern.

COVID-19 infection in dialysis patients is associated with marked depletion of fecal SCFAs and broad perturbations of systemic metabolism, with persistent amino-acid-centered alterations among patients who develop LC. These findings offer a novel metabolic framework supporting the implementation of prolonged follow-up strategies to monitor and ameliorate persistent sequelae in this high-risk population.