Carotenoids and Their Health Benefits as Derived via Their Interactions with Gut Microbiota

Abstract

Carotenoids have been related to a number of health benefits. Their dietary intake and circulating levels have been associated with a reduced incidence of obesity, diabetes, certain types of cancer, and even lower total mortality. Their potential interaction with the gut microbiota (GM) has been generally overlooked but may be of relevance, as carotenoids largely bypass absorption in the small intestine and are passed on to the colon, where they appear to be in part degraded into unknown metabolites. These may include apo-carotenoids that may have biological effects because of higher aqueous solubility and higher electrophilicity that could better target transcription factors, i.e., NF-κB, PPARγ, and RAR/RXRs. If absorbed in the colon, they could have both local and systemic effects. Certain microbes that may be supplemented were also reported to produce carotenoids in the colon. Although some bactericidal aspects of carotenoids have been shown in vitro, a few studies have also demonstrated a prebiotic-like effect, resulting in bacterial shifts with health-associated properties. Also, stimulation of IgA could play a role in this respect. Carotenoids may further contribute to mucosal and gut barrier health, such as stabilizing tight junctions. This review highlights potential gut-related health-beneficial effects of carotenoids and emphasizes the current research gaps regarding carotenoid-GM interactions.

Keywords: Akkermansia spp.; Bifidobacterium spp.; Carotenes; bactericidal effects; carotenoid metabolites; digestion; gut bacteria; inflammation; microbiome; mucosal layer; oxidative stress; xanthophylls.

FIGURE 1

Mechanisms by which carotenoids could interact with the gut mucosa, influencing GM and intestinal barrier properties. GPx, glutathione peroxidase; HO-1, heme-oxygenase 1; IgA, immunoglobulin A; IL-6, interleukin-6; MAPK, mitogen-activated protein kinase; NF-κB, nuclear factor kappa B; Nrf2, nuclear factor erythroid 2–related factor 2; OPG, obligate pathogenic bacteria; PPAR, peroxisome proliferator-activated receptor; ROS, reactive oxygen species; RNS, reactive nitrogen species; SCFA, short-chain fatty acids; SOD-1, superoxide dismutase 1; TLRs, toll-like receptors; TNF-α, tumor necrosis factor alpha.

FIGURE 2

Pathways for biosynthesis of carotenoid precursors. CHK, Choline kinase; CTP, Cytidine 5'-triphosphate; DMAPP, Dimethylallyl disphosphate; Dxp, 1-Deoxy-D-xylulose 5-phosphate; Dxr, 1-Deoxy-D-xylulose 5-phosphate reductoisomerase; Dxs, 1-Deoxy-D-xylulose 5-phosphate synthase; Fd, Ferredoxin; G3P, Glyceraldehyde 3-phosphate; CMP, Cytidine monophosphate; HMBPP, E-4-Hydroxy-3-methyl-but-2-enyl pyrophosphate; HMGR, 3-Hydroxy-3-methylglutaryl-CoA reductase; HmgS, 3-Hydroxy-3-methylglutaryl-CoA synthase; IDI, Isopentenyl diphosphate isomerase; IspD, 2-C-methyl-D-erythritol 4-phosphate cytidylyltransferase; IspE, 4-diphosphocytidyl-2-C-methyl-D-erythritol kinase; IspH, 4-Hydroxy-3-methylbut-2-enyl diphosphate reductase; IPI, Isopentenyl diphosphate isomerase; IMO, Isomalto-oligosaccharides; IPK, Isopentenyl phosphate kinases; IPP, Isopentenyl diphosphate; IspE, CDP-methylerythritol kinase; IUP, Isopentenol utilization pathway; MK, Mevalonate kinase; MVA, Mevalonic acid; MEP, Methylerythritol 4-phosphate; PPi, Pyrophosphate; PMD, Phosphomevalonate decarboxylase; PMK, Phosphomevalonate kinase.

FIGURE 3

Approaches for delivering carotenoids together with probiotics to the colon. IgA, Immunoglobulin A.