PM_2.5 induced neurotoxicity through unbalancing vitamin B12 metabolism by gut microbiota disturbance

ABSTRACT

Fine particulate matter (PM_2.5) in the atmosphere is easily accompanied by toxic and harmful substances, causing serious harm to human health, including cognitive impairment. Vitamin B12 (VitB12) is an essential micronutrient that is synthesized by bacteria and contributes to neurotransmitter synthesis as a nutrition and signaling molecule. However, the relationship between VitB12 attenuation of cognitive impairment and intestinal microbiota regulation in PM_2.5 exposure has not been elucidated. In this study, we demonstrated that PM_2.5 caused behavioral defects and neuronal damage in Caenorhabditis elegans (C. elegans), along with significant gene expression changes in neurotransmitter receptors and a decrease in VitB12 content, causing behavioral defects and neuronal damage in C. elegans. Methylcobalamin (MeCbl), a VitB12 analog, alleviated PM_2.5-induced neurotoxicity in C. elegans. Moreover, using in vivo and in vitro models, we discovered that long-term exposure to PM_2.5 led to changes in the structure of the gut microbiota, resulting in an imbalance of the VitB12-associated metabolic pathway followed by cognitive impairment. MeCbl supplementation could increase the diversity of the bacteria, reduce harmful substance contents, and restore the concentration of short-chain fatty acids (SCFAs) and neurotransmitters to the level of the control group to some degree. Here, a new target to mitigate the harm caused by PM_2.5 was discovered, supplying MeCbl for relieving intestinal and intracellular neurotransmitter disorders. Our results also provide a reference for the use of VitB12 to target the adjustment of the human intestinal microbiota to improve metabolic disorders in people exposed to PM_2.5.

KEYWORDS:

• Vitamin B12
• methylcobalamin
• atmospheric particulate matter
• in vitro colonic simulation system
• gut microbiome
• neurotransmitters

Disclosure statement

No potential conflict of interest was reported by the author(s).

Availability of data and material

All data generated or analyzed during the current study are included in this published article [and supplementary information files] or are available in the NCBI SRA repository, PRJNA889242.

Supplementary material

Supplemental data for this article can be accessed online at https://doi.org/10.1080/19490976.2023.2267186

Additional information

Funding

This research was funded by the National Natural Science Foundation of China (grant number 32072230), Provincial Natural Science Foundation of Zhejiang (grant number LY21C200007) and Zhejiang Gongshang University Elite Funding (3090JYN9921001G).