Changes in the Fecal Metabolome Accompany an Increase in Aberrant Crypt Foci in the Colon of C57BL/6 Mice Fed with a High-Fat Diet
High-fat diet (HFD)-induced obesity is a risk factor for colon cancer. Our previous data show that compared to an AIN-93 diet (AIN), a HFD promotes azoxymethane (AOM)-induced colonic aberrant crypt foci (ACF) formation and microbial dysbiosis in C57BL/6 mice. To explore the underlying metabolic basi...
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| Format: | Article |
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MDPI AG
2022-11-01
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| Series: | Biomedicines |
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| Online Access: | https://www.mdpi.com/2227-9059/10/11/2891 |
| _version_ | 1797465829051203584 |
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| author | Huawei Zeng Bryan D. Safratowich Wen-Hsing Cheng Andrew D. Magnuson Matthew J. Picklo |
| author_facet | Huawei Zeng Bryan D. Safratowich Wen-Hsing Cheng Andrew D. Magnuson Matthew J. Picklo |
| author_sort | Huawei Zeng |
| collection | DOAJ |
| description | High-fat diet (HFD)-induced obesity is a risk factor for colon cancer. Our previous data show that compared to an AIN-93 diet (AIN), a HFD promotes azoxymethane (AOM)-induced colonic aberrant crypt foci (ACF) formation and microbial dysbiosis in C57BL/6 mice. To explore the underlying metabolic basis, we hypothesize that AOM treatment triggers a different fecal metabolomic profile in C57BL/6 mice fed the HFD or the AIN. We found that 65 of 196 identified metabolites were significantly different among the four groups of mice (AIN, AIN + AOM, HFD, and HFD + AOM). A sparse partial least squares discriminant analysis (sPLSDA) showed that concentrations of nine fecal lipid metabolites were increased in the HFD + AOM compared to the HFD, which played a key role in overall metabolome group separation. These nine fecal lipid metabolite concentrations were positively associated with the number of colonic ACF, the cell proliferation of Ki67 proteins, and the abundance of dysbiotic bacteria. These data suggest that the process of AOM-induced ACF formation may increase selective fecal lipid concentrations in mice fed with a HFD but not an AIN. Collectively, the accumulation of these critical fecal lipid species may alter the overall metabolome during tumorigenesis in the colon. |
| first_indexed | 2024-03-09T18:27:09Z |
| format | Article |
| id | doaj.art-31cc5c8cc97d4995afa6b8b935a9ba92 |
| institution | Directory Open Access Journal |
| issn | 2227-9059 |
| language | English |
| last_indexed | 2024-03-09T18:27:09Z |
| publishDate | 2022-11-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Biomedicines |
| spelling | doaj.art-31cc5c8cc97d4995afa6b8b935a9ba922023-11-24T07:45:47ZengMDPI AGBiomedicines2227-90592022-11-011011289110.3390/biomedicines10112891Changes in the Fecal Metabolome Accompany an Increase in Aberrant Crypt Foci in the Colon of C57BL/6 Mice Fed with a High-Fat DietHuawei Zeng0Bryan D. Safratowich1Wen-Hsing Cheng2Andrew D. Magnuson3Matthew J. Picklo4United States Department of Agriculture, Agricultural Research Service, Grand Forks Human Nutrition Research Center, Grand Forks, ND 58203, USAUnited States Department of Agriculture, Agricultural Research Service, Grand Forks Human Nutrition Research Center, Grand Forks, ND 58203, USADepartment of Food Science, Nutrition and Health Promotion, Mississippi State University, Starkville, MS 39762, USAUnited States Department of Agriculture, Agricultural Research Service, Grand Forks Human Nutrition Research Center, Grand Forks, ND 58203, USAUnited States Department of Agriculture, Agricultural Research Service, Grand Forks Human Nutrition Research Center, Grand Forks, ND 58203, USAHigh-fat diet (HFD)-induced obesity is a risk factor for colon cancer. Our previous data show that compared to an AIN-93 diet (AIN), a HFD promotes azoxymethane (AOM)-induced colonic aberrant crypt foci (ACF) formation and microbial dysbiosis in C57BL/6 mice. To explore the underlying metabolic basis, we hypothesize that AOM treatment triggers a different fecal metabolomic profile in C57BL/6 mice fed the HFD or the AIN. We found that 65 of 196 identified metabolites were significantly different among the four groups of mice (AIN, AIN + AOM, HFD, and HFD + AOM). A sparse partial least squares discriminant analysis (sPLSDA) showed that concentrations of nine fecal lipid metabolites were increased in the HFD + AOM compared to the HFD, which played a key role in overall metabolome group separation. These nine fecal lipid metabolite concentrations were positively associated with the number of colonic ACF, the cell proliferation of Ki67 proteins, and the abundance of dysbiotic bacteria. These data suggest that the process of AOM-induced ACF formation may increase selective fecal lipid concentrations in mice fed with a HFD but not an AIN. Collectively, the accumulation of these critical fecal lipid species may alter the overall metabolome during tumorigenesis in the colon.https://www.mdpi.com/2227-9059/10/11/2891aberrant crypt focifatty acidsfecal metabolomelipidobesity |
| spellingShingle | Huawei Zeng Bryan D. Safratowich Wen-Hsing Cheng Andrew D. Magnuson Matthew J. Picklo Changes in the Fecal Metabolome Accompany an Increase in Aberrant Crypt Foci in the Colon of C57BL/6 Mice Fed with a High-Fat Diet Biomedicines aberrant crypt foci fatty acids fecal metabolome lipid obesity |
| title | Changes in the Fecal Metabolome Accompany an Increase in Aberrant Crypt Foci in the Colon of C57BL/6 Mice Fed with a High-Fat Diet |
| title_full | Changes in the Fecal Metabolome Accompany an Increase in Aberrant Crypt Foci in the Colon of C57BL/6 Mice Fed with a High-Fat Diet |
| title_fullStr | Changes in the Fecal Metabolome Accompany an Increase in Aberrant Crypt Foci in the Colon of C57BL/6 Mice Fed with a High-Fat Diet |
| title_full_unstemmed | Changes in the Fecal Metabolome Accompany an Increase in Aberrant Crypt Foci in the Colon of C57BL/6 Mice Fed with a High-Fat Diet |
| title_short | Changes in the Fecal Metabolome Accompany an Increase in Aberrant Crypt Foci in the Colon of C57BL/6 Mice Fed with a High-Fat Diet |
| title_sort | changes in the fecal metabolome accompany an increase in aberrant crypt foci in the colon of c57bl 6 mice fed with a high fat diet |
| topic | aberrant crypt foci fatty acids fecal metabolome lipid obesity |
| url | https://www.mdpi.com/2227-9059/10/11/2891 |
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