Unraveling the mechanisms underlying air pollution-induced dysfunction of the oral–gut–brain axis: implications for human health and well-being

Figures & Tables

Categories		Targets	Reference
Inflammatory response	Pulmonary inflammatory response	MAPK/AP-1, JAK/STAT, NF-κB activation; NLRP3 inflammasome#; TNF-α, IL-1β, IL-6#	[105,106,107,108,109,110]
	Intestinal inflammatory reaction	MMP-9 and TLR4#, Tight junction protein$; Increased intestinal permeability	[86, 111]
	Neuroinflammatory response	The integrity of the BBB destroyed; microglia and astrocytes activated IL-1β#; oAβ# Vitamin B12 metabolism imbalance, neurotoxicity	[112, 113] [114] [115]
Oxidative stress		ROS# MAPK pathway activated ICAM-1#, VCAM-1#, MMPs activated	[114] [116] [117, 118]
Mitochondrial dysfunction		Overproduction of ROS, NOX4/Nrf2 REDOX imbalance, mitochondrial membrane potential reduced Bcl-2#, Bax#, caspase# mTOR activated, LC3#, beclin1# PINK1/parking activated	[119] [120, 121] [122, 123] [124]
Epigenetic changes	DNAm	FOXP3 oral cell promoter methylation Hypomethylation of genomic DNA in lung tissue and abnormal DNAm of IL-4 and IFN-γ ROS-Akt-DNMT3B hypermethylation	[125] [126] [127]
	Histone modification	H3K27me3 $ HDAC2# HDAC2#, Sirtuin 6# H3K9 acetylation# H3K9me2/me3 $, γ-H2A.X #	[128, 129] [130] [131] [132] [97]
	Non-coding RNA	miR-6238, miR-146, miR-139, miR-340# miR-155, lncRNA SOX2-OT ceRNA lncRNA NEAT1# TGF-βR2/miR-466h-3p-IL-17Rα/Aβ-42/Ache and miR-125b-Pcdhgb8 miR-574-5p miR-6315, miR-3588, miR-466b-5p, miR-3560, let-7b-5p#, miR-99b-5p, miR-92b-5p, miR-99a-5p, miR-338-5p, let-7e-5p $	[133, 134] [135] [136] [137]

Air pollutant	Sources	Health effects	Reference
PM2.5	Complex mix of solid and liquid particles	Mouth, intestinal, and nervous system disorders; increased risk of various diseases	[21, 29]
O₃	Highly reactive oxidizing gas	Chronic inflammation; neurodegenerative and intestinal conditions	[31, 32]
SO₂	Burning fuels containing sulfide	Respiratory issues; increased risk of mortality, dental problems, enteritis, and stroke	[33, 36]
NO₂	Burning fossil fuels and vehicle emissions	Mucous membrane damage; increased risk of peptic ulcer bleeding and Parkinson's disease	[39, 42]
CO	Incomplete combustion of hydrocarbons	Tissue oxygen deprivation; increased risk of oral conditions, Sjogren's syndrome, and migraine	[43, 46]
PAHs	Incomplete combustion of organic matter	Toxic, mutagenic, and carcinogenic; increased risk of oral cancer, brain shrinkage, and motor impairments	[48, 58]
Dioxins	Waste burning, chemical production, steel plant operations, vehicle use, and accidental landfill fires	Accumulate in living organisms; increased risk of dental problems, inflammatory bowel conditions, and cognitive decline	[49, 53, 56]
Heavy metals (Chromium, Pb, Hg, Cd)	Various industrial and anthropogenic activities	Renal, cardiovascular, and neurological issues; increased risk of diabetes and cancer	[57, 59]