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Gut microbiota dysbiosis and altered fecal metabolome in patients with age-related cataract

ABSTRACT:

Age-related cataract (ARC) is a leading cause of vision loss whose underlying mechanisms remain incompletely understood. Emerging evidence suggests the gut microbiota can influence ocular health via systemic metabolic and inflammatory pathways, yet the gut–eye connection in cataract has not been explored. We aimed to characterize gut microbial communities and fecal metabolic profiles in ARC patients.

Fecal samples from 30 ARC patients and 30 age- and sex-matched healthy controls were collected and analyzed. Gut microbiota composition was profiled by 16S rDNA gene sequencing, and untargeted fecal metabolomics was performed by liquid chromatography–mass spectrometry (LC–MS). Additionally, eight short-chain fatty acids (SCFAs) were quantified by targeted gas chromatography–mass spectrometry (GC–MS). Differences in microbial taxa and metabolites were identified using multivariate statistics (PCA, PLS-DA/OPLS-DA) and differential abundance testing (VIP>1, p<0.05 after FDR correction).

INSTRUMENT(S): Liquid Chromatography MS - negative - reverse phase, Gas Chromatography MS -, Liquid Chromatography MS - positive - reverse phase

PROVIDER: MTBLS12932 | MetaboLights | 2025-09-03

REPOSITORIES: MetaboLights

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			Action	DRS
	a_MTBLS12932_GC-MS___metabolite_profiling.txt	Txt
	a_MTBLS12932_LC-MS_negative_reverse-phase_metabolite_profiling.txt	Txt
	a_MTBLS12932_LC-MS_positive_reverse-phase_metabolite_profiling.txt	Txt
	i_Investigation.txt	Txt
	m_MTBLS12932_GC-MS___metabolite_profiling_v2_maf.tsv	Tabular

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Project description:Fibromyalgia is a complex disorder whose main symptoms are chronic widespread pain and fatigue, and affects between 0.2 and 6.6% of the world population. Nowadays, there are no molecular biomarkers which could facilitate diagnosis, underlining the extreme necessity of basic research on this chronic disorder. The latest efforts by the researchers have focused on studying problems at the level of central nervous system sensitivity, inflammatory and oxidative disorders, and even imbalances related to the intestinal microbiota. A total of 892 women were initially enrolled in the study. For those fulfilling inclusion criteria, a plasma proteome analysis in blood samples was conducted. Briefly, blood was collected, centrifuged and analyzed by liquid nano-chromatography coupled to tandem mass spectrometry. After the raw data analysis, proteins with statistically significant differential abundance and a fold change over 1.2 (20% increase in fibromyalgia compared with control samples) or under 0.8 (20% decrease in fibromyalgia compared with control samples) in fibromyalgia were selected. For fecal metagenome analysis, fecal samples were collected, homogenized and processed for DNA extraction. Amplicon sequencing of V3–V4 regions from the 16S ribosomal RNA gene was performed using the Illumina MiSeq platform Quality control procedures were implemented using thresholds set at 50,000 reads per sample, Q30 Phred Score and an average trimmed read length of 280bp. The statistical analysis was conducted using R v4.3.2 base packages. After applying exclusion criteria, 242 women (199 patients and 43 age- and environmentally paired healthy individuals) provided plasma and feces samples, as well as properly filled health questionnaires. A total of 30 proteins and 19 taxa were differentially expressed in fibromyalgia patients, and its integration into an algorithm allows to discriminate cases and controls. The multiomic approach for biomarker discovery in this study propose a multifactorial connection between gut microbiota and mitochondria-derived oxidative stress and inflammation. Plasma and fecal multiomics analysis suggest an intricate and multifactorial connection between gut microbiota and mitochondria-derived oxidative stress and inflammation in FM patients, with glyceraldehyde-3-phosphate dehydrogenase and Streptococcus salivarius as leading actors.

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Gut microbiota dysbiosis and altered fecal metabolome in patients with age-related cataract

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