Chronic arsenic exposure affects stromal cells and signaling in the small intestine in a sex-specific manner Original paper
Researched by:
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Divine Aleru
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Divine Aleru
Read MoreI am a biochemist with a deep curiosity for the human microbiome and how it shapes human health, and I enjoy making microbiome science more accessible through research and writing. With 2 years experience in microbiome research, I have curated microbiome studies, analyzed microbial signatures, and now focus on interventions as a Microbiome Signatures and Interventions Research Coordinator.
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Metals
Metals
OverviewHeavy metals play a significant and multifaceted role in the pathogenicity of microbial species. Their involvement can be viewed from two primary perspectives: the toxicity of heavy metals to microbes and the exploitation of heavy metals by microbial pathogens to establish infections and evade the host immune response. Understanding these aspects is critical for both […]
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Divine Aleru
Read More
Researched by:
-
Divine Aleru
ID
Divine Aleru
Read More
Microbiome Signatures identifies and validates condition-specific microbiome shifts and interventions to accelerate clinical translation. Our multidisciplinary team supports clinicians, researchers, and innovators in turning microbiome science into actionable medicine.
Divine Aleru
What was studied?
The study focused on the effects of chronic arsenic exposure on the small intestine, specifically on the stromal cells and signaling pathways. Researchers aimed to investigate how arsenic exposure influences mesenchymal cells like trophocytes and telocytes, which play a key role in regulating the intestinal stem cell niche. The study used a mouse model to analyze the impact of different concentrations of arsenic (33 and 100 ppb) on various stromal markers in the small intestine, including the markers for trophocytes (PdgfraLo, CD81) and telocytes (PdgfraHi, CD201, Gli1).
Who was studied?
The study used transgenic mice (Sox9tm2Crm-EGFP) to examine the effects of arsenic exposure. Eighteen male and 18 female mice were exposed to drinking water containing arsenic at concentrations of 0, 33, and 100 ppb for 13 weeks. These mice were specifically chosen because the Sox9-EGFP transgene allows researchers to track intestinal stem cells and other epithelial cell populations. The sex-specific responses to arsenic exposure were analyzed, which revealed differential effects on stromal cells in the small intestine.
Most important findings
The study revealed significant sex-specific differences in the effects of arsenic exposure on stromal cells within the small intestine. Male mice exposed to arsenic showed increased expression of markers for trophocytes, particularly the PdgfraLo marker. In contrast, female mice exposed to arsenic had higher expression levels of telocyte markers, such as PdgfraHi. Additionally, the study found that arsenic exposure altered the epithelial cell populations, reducing Sox9+ cells, a marker for transit amplifying cells, intestinal stem cells, and enteroendocrine cells.
A more in-depth analysis showed that the trophocyte marker CD81 was significantly reduced in both male and female mice exposed to arsenic, suggesting an impairment in the function of these cells. Furthermore, Grem1, a key protein secreted by trophocytes to regulate stem cell differentiation, showed increased expression in males exposed to arsenic, further indicating the perturbation of the stromal cell function. In females, no such increase was observed, which highlights a sex-dependent response to arsenic exposure.
Key implications
The findings from this study have important implications for understanding how arsenic exposure affects the intestinal environment, particularly in terms of the balance between stromal cells like trophocytes and telocytes. Since these cells play a crucial role in maintaining the intestinal stem cell niche and regulating differentiation, the disruption caused by arsenic exposure could have long-term effects on intestinal health. The study also underscores the need for further investigation into the sex-specific mechanisms that underlie arsenic toxicity. These results suggest that arsenic might contribute to the development of diseases related to gastrointestinal health, particularly through its impact on stromal cells and the disruption of signaling pathways necessary for epithelial cell differentiation and regeneration.
Arsenic (As)
Arsenic can disrupt both human health and microbial ecosystems. Its impact on the gut microbiome can lead to dysbiosis, which has been linked to increased disease susceptibility and antimicrobial resistance. Arsenic's ability to interfere with cellular processes, especially through its interaction with essential metals like phosphate and zinc, exacerbates these effects. By understanding how arsenic affects microbial communities and how these interactions contribute to disease, we can develop more effective interventions, including microbiome-targeted therapies and nutritional strategies, to mitigate its harmful effects.