Abstract
An increased risk of developing colorectal cancer has been associated with exposure to persistent organic pollutants (POPs) and alteration in the gut bacterial community. However, there is limited understanding about the impact of maternal exposure to POPs on colorectal cancer and gut microbiota. This study characterized the influence of exposure to a human relevant mixture of POPs during gestation and lactation on colorectal cancer, intestinal metabolite composition and microbiota in the A/J Min/+ mouse model. Surprisingly, the maternal POP exposure decreased colonic tumor burden, as shown by light microscopy and histopathological evaluation, indicating a restriction of colorectal carcinogenesis. 1H nuclear magnetic resonance spectroscopy-based metabolomic analysis identified alterations in the metabolism of amino acids, lipids, glycerophospholipids and energy in intestinal tissue. In addition, 16S rRNA sequencing of gut microbiota indicated that maternal exposure modified fecal bacterial composition. In conclusion, the results showed that early-life exposure to a mixture of POPs reduced colorectal cancer initiation and promotion, possibly through modulation of the microbial and biochemical environment. Further studies should focus on the development of colorectal cancer after combined maternal and dietary exposures to environmentally relevant low-dose POP mixtures.
Highlights
Persistent organic pollutants (POPs) are recognized as a global threat to human health and ecosystems due to their persistence in the environment, accumulation, long-range transport and deleterious effects (Secretariat of the Stockholm Convention, 2008; United Nations Environment Programme, 2019)
The concentrations of polychlorinated biphenyls (PCBs), organochlorine pesticides (OCPs), brominated flame retardants (BFRs) and perfluoroalkylated substances (PFASs) in 20-weekold A/J multiple intestinal neoplasia (Min)/þ mice are presented in Table 1 and in Supplementary Table A5
The present study investigated if maternal exposure to a human relevant mixture of POPs could influence the development of colorectal cancer, intestinal metabolite composition and microbiota in A/J Min/þ mice
Summary
Persistent organic pollutants (POPs) are recognized as a global threat to human health and ecosystems due to their persistence in the environment, accumulation, long-range transport and deleterious effects (Secretariat of the Stockholm Convention, 2008; United Nations Environment Programme, 2019). Many POPs have been shown to cross the placental barrier (Barr et al, 2007; Vizcaino et al, 2014; Winkens et al, 2017). Exposures to these compounds are initiated during the early prenatal period. Human exposure to POPs has been associated with an increased risk of developing breast (Høyer et al, 2000; Arrebola et al, 2015; Morgan et al, 2016), testicular (McGlynn et al, 2008; Giannandrea et al, 2011) and colorectal cancer (CRC) (Howsam et al, 2004; Lee et al, 2018; Abolhassani et al, 2019). Maternal POP exposure has been shown to increase mammary, ovarian and hepatic tumorigenesis (Cameron and Foster, 2009; Filgo et al, 2015), and direct exposure increased the growth of colorectal tumors (Song et al, 2014; Hansen et al, 2018)
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