Biology subjects

Midya, V.

Publications and source records attributed to Midya, V..

4 recordsLinked to original sources

bioRxiv2025

Zinc and Cobalt exposure influence Akkermansia muciniphila growth and short-chain fatty acid metabolism

Akkermansia muciniphila is a probiotic bacterium that has been proposed as a potential intervention for depression. A. muciniphila is a common mucin degrader, producing short fatty chain acids (SCFAs), including acetate, butyrate, and propionate, which can help regulate mood via the gut-brain axis. However, the interplay between A. muciniphila and other neuroactive environmental exposures is unclear. The objective of this study was to assess the effects of Zn and Co exposure, individually and together, on A. muciniphila growth and SCFA production. Minimum Inhibitory Concentration (MIC) was calculated for each metal, and sub-MIC exposure testing at high and low levels was conducted with single and combined metals. Growth curves were measured for each exposure condition, and SCFAs were measured using liquid chromatography-mass spectroscopy. Growth and SCFA production were compared between exposures and controls using paired t-tests and linear regression models. All p-values were corrected using FDR adjustments (q-values). A. muciniphila was tolerant to both metal exposures, with MICs at 750mg/L for Zn and 4,000 mg/L for Co. Growth at 24-and 48-hours was only significantly reduced upon exposure to high levels of Co, alone and in combination with Zn. Production of propionate significantly increased with high and low Zn exposures alone and in combination with low Co exposure (q-values <0.01), and significantly decreased with high Co exposure alone and in combination with Zn (q-values <0.01). Overall, A. muciniphila was metal tolerant, supporting its use as a probiotic in the presence of other neuroactive metal exposures.

microbiology↗

bioRxiv2025

Primary tumor microbiomes predict distant metastasis of colorectal cancer

Metastasis causes most cancer-related deaths in colorectal carcinoma (CRC), and microbiome markers may have prognostic value. We hypothesized that primary tumor microbiomes predict distant metastases. We analyzed 5-year metastasis-free survival (MFS) in a retrospective cohort of 900 ORIEN CRC tumor microbiomes (RNAseq). ORIEN findings were validated on an independent cohort using 16S rDNA sequencing and pathobiont-specific qPCR. Microbiome alpha diversity was higher in primary tumors than metastases and positively correlated with metastasis risk. Microbiome beta diversity distinguished primary vs. metastasis and predicted 5-year MFS. High primary tumor abundance of B. fragilis and low F. nucleatum were associated with short MFS. Enterobacteriaceae, including E. coli, were enriched in metastases. qPCR identified increased enterotoxigenic B. fragilis and pks+ E. coli detection in CRC metastasizers. Microbial co-occurrence analysis identified a 3-species clique that predicts metastasis (OR 1.9 [1.4-2.6]). Results suggest that primary tumor microbiomes and specific pathobionts are precision markers for metastasis risk.

cancer biology↗

bioRxiv2024

High-dimensional mediation analysis to elucidate the role of metabolites in the association between PFAS exposure and reduced SARS-CoV-2 IgG in pregnancy

We previously found that per- and polyfluoroalkyl substances (PFAS) mixture exposure is inversely associated with SARS-CoV-2 IgG (IgG) antibody levels in pregnant individuals. Here, we aim to identify metabolites mediating this relationship to elucidate the underlying biological pathways. This cross-sectional study included 59 pregnant participants from a US-based pregnancy cohort. Untargeted metabolomic profiling was performed using Liquid Chromatography-High Resolution Sass spectrometry (LC-HRMS), and weighted Quantile Sum (WQS) regression was applied to assess the PFAS and metabolites mixture effects on IgG. Metabolite indices positively or negatively associated with IgG levels were constructed separately and their mediation effects were examined independently and jointly. The PFAS- index was negatively associated with IgG levels (beta=-0.315, p<0.001), with PFHpS and PFHxS as major contributors. Two metabolite-indices were constructed, one positively (beta=1.249, p<0.001) and one negatively (beta=-1.200, p<0.001) associated with IgG. Key contributors for these indices included trigonelline, adipate, p-octopamine, and n-acetylproline. Analysis of a single mediator showed that 74.6% (95% CI: 45.9%, 98.0%) and 68.6% (95% CI: 41.8%, 94.1%) of the PFAS index-IgG total effect were mediated by the negative and positive metabolites-indices, respectively. Joint analysis of the metabolite-indices indicated a cumulative mediation effect of 83.8% (95% CI: 58.1%, 98.7%). Enriched pathways associated with these metabolites indices were phenylalanine, tyrosine, and tryptophan biosynthesis and arginine metabolism. We observed significant mediation effects of plasma metabolites on the PFAS-IgG relationship, suggesting that PFAS is associated with alteration in the balance of plasma metabolites that contributes to reduced plasma IgG production.

bioinformatics↗

bioRxiv2022

Cysteine Restriction-Specific Effects of Sulfur Amino Acid Restriction on Lipid Metabolism

Decreasing dietary intake of methionine exerts robust anti-adiposity effects in rodents but modest effects in humans. Since cysteine can be synthesized from methionine, animal diets are formulated by decreasing methionine and eliminating cysteine. Such diets exert both methionine restriction (MR) and cysteine restriction (CR), i.e., sulfur amino acid restriction (SAAR). Contrarily, human diets used in clinical studies did not eliminate cysteine and thus might have exerted only MR. Epidemiological studies positively correlate body adiposity with plasma cysteine but not with methionine, suggesting that CR, but not MR, is responsible for the antiadiposity effects of SAAR in rodents. Whether this is true, and if so, the underlying mechanisms are unknown. Using multiple diets with variable concentrations of methionine and cysteine, we demonstrate that the anti-adiposity effects of SAAR are due to CR. CR increased serinogenesis (serine biosynthesis from non-glucose substrates) by diverting substrates from glyceroneogenesis, essential for fatty acid/triglyceride cycling. Molecular data suggest that the CR results in glutathione depletion, which induces Nrf2 and downstream targets Phgdh (the serine biosynthetic enzyme) and Pepck-M. Using multiple mouse models, we show that the magnitude of SAAR-induced changes in molecular markers depends on dietary fat concentration (60 fat>10% fat), gender (males>females), and age-at-onset (young>adult). Our findings are translationally relevant as we found a negative correlation of plasma serine with triglycerides and metabolic syndrome criteria in a cross-sectional epidemiological study. SAAR-like diets with high polyunsaturated fatty acids increased plasma serine in a short-term human feeding study. Serinogenesis might be a potential target to correct hypertriglyceridemia.

biochemistry↗