The Human Fecal Microbiota Metabolizes Foodborne Heterocyclic Aromatic Amines by Reuterin Conjugation and Further Transformations

Abstract

Scope: Heterocyclic aromatic amines (HAAs) are process-induced food contaminants with high mutagenic and/or carcinogenic potential. Although the human gut microbiota is known to affect the metabolism of dietary constituents, its impact on HAA metabolism and toxicity has been little studied. Here, the glycerol-dependent metabolism of seven foodborne HAAs (AαC, Trp-P-1, harman, norharman, PhIP, MeIQx, and MeIQ) by the human fecal microbiota is investigated. Methods and results: As analyzed by HPLC-DAD/FLD, the extent of conversion is strongly dependent on glycerol supplementation and HAA structure. AαC (60-100%) and the 2-aminoimidazoazarenes (up to 58%) are especially prone to microbial conversion. Based on high-resolution MS and/or NMR spectroscopy data, 70 fecal metabolites are identified in total, mainly formed by chemical reactions with one or two molecules of microbially derived reuterin. Moreover, it has been demonstrated that the human fecal microbiota can further transform reuterin adducts by reduction and/or hydroxylation reactions. Upon isolation, some reuterin-induced HAA metabolites appear to be partially unstable, complicating structural identification. Conclusion: The formation of microbial metabolites needs to be incorporated into risk assessment considerations for HAAs in human health. In this study, several HAA metabolites, mainly reuterin-dependent, are identified in vitro, providing the basis for future human studies investigating microbial HAA metabolism.

Impact of manipulation of glycerol/diol dehydratase activity on intestinal microbiota ecology and metabolism

“…Acrolein conjugation with HCA appears to reduce mutagenicity (Zhang et al ., 2017; Zhang et al ., 2019a), and this conjugation process has been also demonstrated for several abundant HCA other than PhIP (Beer et al ., 2019), suggesting that microbial‐produced acrolein might attenuate initiation of colorectal carcinogenesis. However, due to the high reactivity of acrolein, it has been anticipated that the concentration necessary to transform 100–200 nM of PhIP or other HCA is likely several magnitudes higher (Engels et al ., 2016b; Zhang et al ., 2017; Zhang et al ., 2019b).…”

Acute Ecotoxicological and Histopathological Effects of Maxilon Blue 5G as an Azo Dye on Earthworms

“…Intestinal microflora of humans and animal species can decrease azo groups of xenobiotics (Cerniglia et al, 1982). The decline reaction is responsible for the manufacture of aromatic amines with carcinogenic and mutagenic effects (Govindwar et al, 2014;Beer et al, 2019). Bacterial degradation of azo dyes has generally been reported when tearing of nitrogen bonds is initiated by the biotransformation process of the azo reductase enzyme (Zanoni et al, 2013;Franco et al, 2018).…”

Enterochromaffin Cells: Sentinels to Gut Microbiota in Hyperalgesia?

“…Among them, at least TRPV1-4, TRPM8 and TRPA1 are expressed in nociceptive sensory neurons, which transfer thermal, chemical, and mechanical stimulation signals, playing an important role in the occurrence and development of pathological pain perception (Dai, 2016). TRPV1 (Deng et al, 2021), TRPV5 and 6 (Hua et al, 2019), TRPM7 (Lv et al, 2020) and 8 (Wen et al, 2020), TRPA1 (Pagano et al, 2019), TRPP1 (Beer et al, 2019) have all been found to have some associations with the gut microbiota, but so far only the TRPA1 receptor has been studied in ECs (Nozawa et al, 2009). TRPA1 is a chemoreceptor widely expressed in humans and animals, including dorsal root ganglia, bladder, gastrointestinal tract, skin, respiratory tract, blood vessels, etc.…”