Foodborne
carbon dots (CDs) are generally produced during cooking
and exist in food items. Generally, CDs are regarded as nontoxic materials,
but several studies have gradually confirmed the cytotoxicity of CDs,
such as oxidative stress, reduced cellular activity, apoptosis, etc.
However, studies focusing on the health effects of long-term intake
of food-borne CDs are scarce, especially in populations susceptible
to metabolic disease. In this study, we reported that CDs in self-brewing
beer had no effect on glucose metabolism in CHOW-fed mice but exacerbated
high-fat-diet (HFD)-induced glucose metabolism disorders via the gut-liver
axis. Chronic exposure to foodborne CDs increased fasting glucose
levels and exacerbated liver and intestinal barrier damage in HFD-fed
mice. The 16s rRNA sequencing analysis revealed that CDs significantly
altered the gut microbiota composition and promoted lipopolysaccharide
(LPS) synthesis-related KEGG pathways (superpathway of (Kdo)2-lipid
A, Kdo transfer to lipid IVA Ill (Chlamydia), lipid IVA biosynthesis,
and so on) in HFD-fed mice. Mechanically, CD exposure increased the
abundance of Gram-negative bacteria (Proteobacteria and Desulfovibrionaceae), thus producing excessive
endotoxin-LPS, and then LPS was transferred by the blood circulation
to the liver due to the damaged intestinal barrier. In the liver,
LPS promoted TLR4/NF-κB/P38 MAPK signaling, thus enhancing systemic
inflammation and exacerbating HFD-induced insulin resistance. However,
pretreating mice with antibiotics eliminated these effects, indicating
a key role for gut microbiota in CDs exacerbating glucose metabolism
disorders in HFD-fed mice. The finding herein provides new insight
into the potential health risk of foodborne nanoparticles in susceptible
populations by disturbing the gut-liver axis.