3,3´-Diindolylmethane Suppresses the Inflammatory Response to Lipopolysaccharide in Murine Macrophages3

Cho, Han Jin; Seon, Mi Ra; Lee, Yeo Myeong; Kim, Jaebong; Kim, Jin‐Kyung; Kim, Sang Geon; Park, Jung Han Yoon

doi:10.1093/jn/138.1.17

Cited by 113 publications

(88 citation statements)

References 44 publications

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“…Whereas data presented here show protective effects of E. coli K12 versus K12ΔtnaA, recent data suggest that other intestinal eubacteria, including many Bacteroides and Lactobacillus species, likewise use TnaA to produce protective indole derivatives, including ICA and indole-3-carbinol (I3C)) (16,(48)(49)(50). Responsiveness to particular indoles may differ and be tuned to the precise complement of indoles produced by the microbiota.…”

Section: Discussioncontrasting

confidence: 56%

Indoles from commensal bacteria extend healthspan

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et al. 2017

Proc. Natl. Acad. Sci. U.S.A.

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Multiple studies have identified conserved genetic pathways and small molecules associated with extension of lifespan in diverse organisms. However, extending lifespan does not result in concomitant extension in healthspan, defined as the proportion of time that an animal remains healthy and free of age-related infirmities. Rather, mutations that extend lifespan often reduce healthspan and increase frailty. The question arises as to whether factors or mechanisms exist that uncouple these processes and extend healthspan and reduce frailty independent of lifespan. We show that indoles from commensal microbiota extend healthspan of diverse organisms, including Caenorhabditis elegans, Drosophila melanogaster, and mice, but have a negligible effect on maximal lifespan. Effects of indoles on healthspan in worms and flies depend upon the aryl hydrocarbon receptor (AHR), a conserved detector of xenobiotic small molecules. In C. elegans, indole induces a gene expression profile in aged animals reminiscent of that seen in the young, but which is distinct from that associated with normal aging. Moreover, in older animals, indole induces genes associated with oogenesis and, accordingly, extends fecundity and reproductive span. Together, these data suggest that small molecules related to indole and derived from commensal microbiota act in diverse phyla via conserved molecular pathways to promote healthy aging. These data raise the possibility of developing therapeutics based on microbiota-derived indole or its derivatives to extend healthspan and reduce frailty in humans.C. elegans | aging | frailty | aryl hydrocarbon receptor | microbiota R ecent advances in health care have contributed to a significant increase in life expectancy of individuals, especially in developed countries, which predict an expansion of geriatric populations by as much as 350-fold over the next 40 y (1). However, extension of lifespan is often accompanied by increased frailty, and attendant increases in global healthcare expenditures are expected to be both massive and unsustainable (2). Such data highlight the need to develop means to extend healthspan, which is broadly defined as the length of time that an individual remains healthy and free of age-related infirmities (3, 4).Healthspan has often been convolved with lifespan, and extended healthspan has been associated with slowed onset of normal age-related changes (e.g., sarcopenia). Thus, mutations that extend lifespan might be expected to likewise extend healthspan. Recent studies in Caenorhabditis elegans indicate that, relative to wild-type animals, mutations that extend lifespan do indeed extend the period of youthfulness, in which animals are motile and resistant to bacterial infection (healthspan), but also extend the period of decrepitude or frailty, where animals are relatively immobile (5, 6) Other studies in C. elegans that take into account multiple measures of health, each normalized to maximal lifespan, indicate that mutations or conditions that extend lifespan minimally impact or ev...

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Section: Discussioncontrasting

confidence: 56%

Indoles from commensal bacteria extend healthspan

Sonowal

Swimm

Sahoo

et al. 2017

Proc. Natl. Acad. Sci. U.S.A.

147

157

View full text Add to dashboard Cite

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“…Similar to that for SF, a role for I3C in controlling inflammation is emerging (Cho et al 2008). Diindolyl methane was seen to decrease not only TNFa, IL6 and IL-1b release, but also NF-jB and iNOS activation in activated Raw 264.7 macrophages.…”

Section: Cardiovascular and Possible Cns Protection By Sulforaphane Amentioning

confidence: 68%

Physiological effects of broccoli consumption

2008

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Epidemiological studies suggest that broccoli can decrease risk for cancer. Broccoli contains many bioactives, including vitamins C and E, quercetin and kaempferol glycosides and, like other members of the Brassicaceae, several glucosinolates, including glucobrassicin (3-indolylmethyl glucosinolate) and glucoraphanin (4-methylsulphinylbutyl glucosinolate). A key bioactive component responsible for much of this activity may be sulforaphane (1-isothiocyanato-4-methylsulfinylbutane), a hydrolysis product of glucoraphanin. Sulforaphane not only upregulates a number of phase II detoxification enzymes involved in clearance of chemical carcinogens and reactive oxygen species, but has anti-tumorigenic properties, causing cell cycle arrest and apoptosis of cancer cells. The bioequivalency of sulforaphane and whole broccoli have not been fully evaluated, leaving it unclear whether whole broccoli provides a similar effect to purified sulforaphane, or whether the presence of other components in broccoli, such as indole-3-carbinol from glucobrassicin, is an added health benefit. Dietary indole-3-carbinol is known to alter estrogen metabolism, to cause cell cycle arrest and apoptosis of cancer cells and, in animals, to decrease risk for breast cancer. Recent research suggests that both dietary broccoli and the individual components sulforaphane and indole-3-carbinol may offer protection from a far broader array of diseases than cancer, including cardiovascular and neurodegenerative diseases. A common link between these oxidative degenerative diseases and cancer may be aggravation by inflammation. A small body of literature is forming suggesting that both indole-3-carbinol and sulforaphane may protect against inflammation, inhibiting cytokine production. It remains to be seen whether cancer, cardiovascular disease, dementia and other diseases of aging can all benefit from a diet rich in broccoli and other crucifers.

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“…However, it is not the only transcription factor involved in regulating these genes. In fact, it frequently functions together with other transcription factors, such as AP-1, that are also involved in the regulation of inflammatory and immune genes [19]. Many of the genes involved in the acute inflammatory responses in the atherogenic process are potently activated by the transcription factors NFkB and AP-1 [18].…”

Section: Discussionmentioning

confidence: 99%