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Published on: November 17, 2018
Arsenic-Containing Medicine Treatment Disturbed the Human Intestinal Microbial Flora
Jiaojiao Li1, Xinshuo Chen1, Shixiang Zhao2
1College of Ecology and Environmental Sciences & Yunnan Key Laboratory for Plateau Mountain Ecology and Restoration of Degraded Environments, Yunnan University, Kunming 650500, China.
Abstract:
Human intestinal microbiome plays vital role in maintaining intestinal homeostasis and interacting with xenobiotics. Few investigations have been conducted to understand the effect of arsenic-containing medicine exposure on gut microbiome. Most animal experiments are onerous in terms of time and resources and not in line with the international effort to reduce animal experiments. We explored the overall microbial flora by 16S rRNA genes analysis in fecal samples from acute promyelocytic leukemia (APL) patients treated with arsenic trioxide (ATO) plus all-trans retinoic acid (ATRA). Gut microbiomes were found to be overwhelmingly dominated by Firmicutes and Bacteroidetes after taking medicines containing arsenic in APL patients. The fecal microbiota composition of APL patients after treatment showed lower diversity and uniformity shown by the alpha diversity indices of Chao, Shannon, and Simpson. Gut microbiome operational taxonomic unit (OTU) numbers were associated with arsenic in the feces. We evaluated Bifidobacterium adolescentis and Lactobacillus mucosae to be a keystone in APL patients after treatment. Bacteroides at phylum or genus taxonomic levels were consistently affected after treatment. In the most common gut bacteria Bacteroides fragilis, arsenic resistance genes were significantly induced by arsenic exposure in anaerobic pure culture experiments. Without an animal model, without taking arsenicals passively, the results evidence that arsenic exposure by drug treatment is not only associated with alterations in intestinal microbiome development at the abundance and diversity level, but also induced arsenic biotransformation genes (ABGs) at the function levels which may even extend to arsenic-related health outcomes in APL.
Insights
Arsenic-based cancer treatments alter the gut microbiome in acute promyelocytic leukemia (APL) patients, reducing diversity and inducing arsenic resistance genes. This highlights potential impacts on health outcomes.
Area of Science:
- Microbiology
- Toxicology
- Oncology
Background:
- The human gut microbiome is crucial for homeostasis and xenobiotic metabolism.
- Limited research exists on arsenic-containing medications' effects on the gut microbiome.
- Reducing animal testing is an international priority.
Purpose of the Study:
- To investigate the impact of arsenic trioxide (ATO) plus all-trans retinoic acid (ATRA) on the gut microbiome of acute promyelocytic leukemia (APL) patients.
- To analyze changes in microbial flora and identify key bacterial species and functional genes.
- To establish a non-animal model approach for studying arsenic exposure effects.
Main Methods:
- 16S rRNA gene sequencing of fecal samples from APL patients undergoing ATO + ATRA treatment.
- Alpha diversity analysis (Chao, Shannon, Simpson indices) to assess microbial diversity and uniformity.
- Anaerobic pure culture experiments to evaluate arsenic resistance gene induction in *Bacteroides fragilis*.
Main Results:
- Gut microbiomes were dominated by Firmicutes and Bacteroidetes post-treatment.
- APL patients exhibited reduced microbial diversity and uniformity.
- Arsenic in feces correlated with gut microbiome operational taxonomic unit (OTU) numbers.
- *Bifidobacterium adolescentis* and *Lactobacillus mucosae* were identified as keystone species.
- Bacteroides were consistently affected at phylum and genus levels.
- Arsenic exposure significantly induced arsenic biotransformation genes (ABGs) in *Bacteroides fragilis*.
Conclusions:
- Arsenic-containing drug treatment in APL patients significantly alters gut microbiome composition, diversity, and function.
- Induced arsenic biotransformation genes (ABGs) suggest a functional response to arsenic exposure within the gut.
- These microbiome alterations and functional changes may have implications for arsenic-related health outcomes in APL patients.
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