Naturalizing laboratory mice by housing in a farmyard-type habitat confers protection against colorectal carcinogenesis.

Living in a farm environment in proximity to animals is associated with reduced risk of developing allergies and asthma, and has been suggested to protect against other diseases, such as inflammatory bowel disease and cancer. Despite epidemiological evidence, experimental disease models that recapitulate such environments are needed to understand the underlying mechanisms. In this study, we show that feralizing conventional inbred mice by continuous exposure to a livestock farmyard-type environment conferred protection toward colorectal carcinogenesis. Two independent experimental approaches for colorectal cancer induction were used; spontaneous (Apc Min/+ mice on an A/J background) or chemical (AOM/DSS). In contrast to conventionally reared laboratory mice, the feralized mouse gut microbiota structure remained stable and resistant to mutagen- and colitis-induced neoplasia. Moreover, the feralized mice exhibited signs of a more mature immunophenotype, indicated by increased expression of NK and T-cell maturation markers, and a more potent IFN-γ response to stimuli. In our study, hygienically born and raised mice subsequently feralized post-weaning were protected to a similar level as life-long exposed mice, although the greatest effect was seen upon neonatal exposure. Collectively, we show protective implications of a farmyard-type environment on colorectal cancer development and demonstrate the utility of a novel animal modeling approach that recapitulates realistic disease responses in a naturalized mammal.

Induction of colorectal carcinogenesis in the C57BL/6J and A/J mouse strains with a reduced DSS dose in the AOM/DSS model.

BACKGROUND: Colorectal cancer (CRC) is one of the most frequently diagnosed cancers worldwide and thus mouse models of CRC are of significant value to study the pathogenesis. The Azoxymethane/Dextran sulfate sodium (AOM/DSS) model is a widely used, robust initiation-promotion model for chemical induction of colitis-associated CRC in rodents. However, the dosage of chemicals, treatment regimens and outcome measures vary greatly among studies employing this model. Thus, the aim of this study was to examine an AOM/DSS model involving a reduced (1%) dose of DSS for induction of carcinogenesis in A/J and C57BL/6J (B6) mice. RESULTS: We show that colonic preneoplastic lesions can be reliably detected in A/J and B6 mice by use of a AOM/DSS model involving a single injection of 10 mg/kg AOM followed by three 7-day cycles of a low-dose (1%) DSS administration. Supporting existing evidence of A/J mice exhibiting higher susceptibility to AOM than B6 mice, our AOM/DSS-treated A/J mice developed the highest number of large colonic lesions. Clinical symptoms in both strains subjected to the AOM/DSS treatment did not persist in-between treatment cycles, demonstrating that the animals tolerated the treatment well. CONCLUSIONS: Our findings suggest that a reduced dose of DSS in the AOM/DSS model can be considered in future studies of early phase colorectal carcinogenesis in the A/J and B6 mouse strains using preneoplastic lesions as an outcome measure, and that such regimen may reduce the risk of early trial terminations to accommodate human endpoints. Overall, our data emphasize the importance of devoting attention towards choice of protocol, outcome measures and mouse strain in studies of CRC in mice according to the study purpose.

The Influence of Persistent Organic Pollutants on Thyroidal, Reproductive and Adrenal Hormones After Bariatric Surgery.

INTRODUCTION: Persistent organic pollutants (POPs) including organochlorine pesticides, polychlorinated biphenyls (PCBs), and per- and polyfluoroalkylated substances (PFASs) are suspected endocrine disruptors. AIM: To evaluate the associations between POPs and thyroidal, reproductive, and adrenal hormones in a study population treated with bariatric surgery. METHODS: Blood samples from a cohort of 63 participants before and 1 year after bariatric surgery were analyzed for 16 lipophilic POPs, 17 PFASs, and thyroidal, reproductive, and adrenal hormones. Participants reporting relevant medical conditions or interfering medication were excluded, and plausible confounders were corrected for in multiple regression analyses. RESULTS: Free thyroxine (fT4) showed a significant decrease from preoperative to postoperative follow-up, and regression analyses demonstrated that p,p'-dichlorodiphenyldichloroethylene (p,p-DDE) was inversely associated with the ratio free triiodothyronine/free thyroxine (fT3/fT4). Testosterone concentrations in male participants increased significantly in the study period, and sex hormone-binding globulin (SHBG) increased in both gender. Regression analyses showed positive associations between increased levels of lipophilic POPs and the raised postoperative testosterone and SHBG concentrations in males. For females, an inverse association between the sum perfluoroalkyl carboxylic acids (ΣPFCA) and SHBG was seen. Regression analyses of postoperative serum cortisol concentrations on changes in hexachlorobenzene (HCB) showed a non-significant inverse association. CONCLUSION: The results suggest that POPs may have an influence on the hypothalamic-pituitary-thyroid (HPT) and the hypothalamic-pituitary-gonadal (HPG) axes after bariatric surgery. Because of small sample sizes and discrepancy in the sampling time points pre- and postoperatively, the observed hormonal impacts of POPs must be interpreted as associative and not causative. Further studies are needed to confirm the findings.

Occurrence and levels of persistent organic pollutants (POPs) in farmed and wild marine fish from Tanzania. A pilot study.

In 2016, farmed and wild milkfish (Chanos chanos) and mullet (Mugil cephalus) from Tanzania mainland (Mtwara) and Zanzibar islands (Pemba and Unguja) were collected for analyses of persistent organic pollutants (POPs). Fish livers were analysed for organochlorine pesticides (OCPs), polychlorinated biphenyls (PCBs), brominated flame retardants (BFRs). Muscle tissue was used for analyses of perfluoroalkyl substances (PFASs). The major contaminant was p,p'-DDE. The highest p,p'-DDE concentration was found in wild milkfish from Mtwara (715.27 ng/g lipid weight (lw)). This was 572 times higher than the maximum level detected in farmed milkfish from the same area. The ratios of p,p'-DDE/p,p'-DDT in wild milkfish and mullet from Mtwara and Pemba indicate historical use of DDT. In contrast, ratios in farmed milkfish from Unguja and Mtwara, suggest recent use. The levels of HCB, HCHs and trans-nonachlor were low. ∑10PCBs levels were low, ranging from  -180> -138. PBDEs were detected in low and varying levels in all locations. BDE-47 was the dominating congener, and the highest level was found in farmed milkfish from Jozani (1.55 ng/g lw). HBCDD was only detected in wild mullet from Pemba at a level of 16.93 ng/g lw. PFAS was not detected in any of the samples. POP levels differed between geographic areas and between farmed and wild fish. Human activities seem to influence levels on PCBs and PBDEs on Unguja.