Proteomics

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Investigation of the human-gut-kidney axis by fecal proteomics, highlights molecular mechanisms affected in the later stages of CKD


ABSTRACT: The interplay of gut microbiota with the kidney system, characteristic to reduced kidney function and increased concentrations of urea in gut; in turn increases bacterial urease activity and generation of uremic toxins. Knowledge on these underlying bidirectional molecular mechanisms is nevertheless still limited. In this exploratory study, fecal proteomics analysis was performed, to investigate this largely unexplored biological material as a source of relevant information reflecting the gut-kidney axis at protein level. Specifically, fecal suspension samples from patients with chronic kidney disease (CKD); CKD1 (n = 12) and CKD4 (n = 17) were analysed by high resolution LC-MS/MS. Protein identification was performed using both the human and bacterial UniProt RefSeq reviewed databases, identifying 701 and 1011 unique proteins, respectively. Differential expression analysis (CKD4/CKD1) revealed significance for human proteins previously associated with reduced saccharolytic fermentation, inflammation and CKD, including pancreatic alpha-amylase and galectin-3-binding protein. Significant changes in bacterial proteins such as glyceraldehyde-3-phosphate dehydrogenase, suggest differential butyrate synthesis in CKD4/CKD1. Quantitatively measured decrease of pancreatic alpha-amylase and butyrate in CKD4/CKD1, supported these hypotheses. In conclusion, this analysis highlighted the presence of inflammation and suggested reduced saccharolytic fermentation affecting butyrate synthesis pathways in later disease stages. Validation by a multi-omics analysis is planned.

INSTRUMENT(S): Q Exactive

ORGANISM(S): Homo Sapiens (human)

SUBMITTER: Sonnal Lohia  

LAB HEAD: Dr Antonia Vlahou

PROVIDER: PXD048778 | Pride | 2025-06-02

REPOSITORIES: Pride

Dataset's files

Source:
Action DRS
221215L000007_fecal_9.mgf Mgf
221215L000007_fecal_9.raw Raw
221215L000007_fecal_9_bacteria.msf Msf
221215L000007_fecal_9_bacteria.mzid.gz Mzid
221215L000007_fecal_9_human.msf Msf
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Investigation of the human-gut-kidney axis by fecal proteomics, highlights molecular mechanisms affected in CKD.

Lohia Sonnal S   Valkenburg Sophie S   Stroggilos Rafael R   Lygirou Vasiliki V   Makridakis Manousos M   Zoidakis Jerome J   Verbeke Francis F   Glorieux Griet G   Vlahou Antonia A  

Heliyon 20240611 12


<h4>Objective</h4>The interplay of gut microbiota with the kidney system in chronic kidney disease (CKD), is characterized by increased concentrations of uric acid in the gut, which in turn, may increase bacterial uricase activity and may lead to the generation of uremic toxins. Nevertheless, knowledge on these underlying bidirectional molecular mechanisms is still limited.<h4>Methods</h4>In this exploratory study, proteomic analysis was performed on fecal samples, targeting to investigate this  ...[more]

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