Metabolites are substances that are formed within our bodies that help us live and grow. Examples include glucose and vitamin D. When changes happen in our bodies, like when we get sick, these metabolites can change. By studying metabolite changes, using a method called metabolomics, we can learn a lot about diseases, what causes them, and how to avoid them. We know that eating foods like fish, fruits, and vegetables is healthy. Eating too much red and processed meat, however, increases our chances of developing certain types of cancer. Unfortunately, we still do not understand why that is. It could be that there are unhealthy, toxic elements or substances in the meat itself or that there are toxic metabolites formed during or after the digestion of red and processed meat. To find out, we must journey into the gut, using metabolomics!
Metabolites: The Link Between Food and Health?
We all know that food is essential because it provides us with the energy and building blocks necessary to live and grow. After food is chewed and swallowed, it is digested and broken down into energy and nutrients in the stomach, small and large intestines, followed by absorption. Healthy foods, like whole grains, fish, fruits, and vegetables, provide our bodies with lots of helpful substances. Unfortunately, not all foods are healthy. Certain foods can also contain harmful, toxic substances or can lead to the formation of toxic metabolites during or following digestion. Metabolites are the intermediate or end product of metabolism, involved in the chemical reactions by which your body converts food into energy. Generally, the amount of harmful metabolites in one meal is too small to instantly make us sick. But, if we eat too much of these unhealthy foods too often, long-term exposure to toxic metabolites may lead to the development certain diseases.
One example of such a disease is colorectal cancer. In this form of cancer, dangerous tumors form in the gut, particularly in the colon and the rectum. The risk of developing colorectal cancer is linked to family history, smoking, and an unhealthy diet and lifestyle, including eating too much red meat (like beef and pork) and processed meat (like ham, meatballs, luncheon meat, sausages, and bacon). It is important to note that eating a lot of white meat, like chicken or turkey, is not linked to colorectal cancer.
Why Do Red and Processed Meats Cause Cancer?
Scientists are convinced that eating too much red and processed red meat leads to the formation of harmful metabolites in the gut. We, however, still do not know which metabolites are formed exactly and how this leads to cancer. That is why we set up a study to investigate which metabolites are formed when we consume meals that contain different types of meat. This was done using metabolomics. Metabolomics is a method that allows us to measure the types and amounts of metabolites that are present in for example a stool sample, enabling us to observe which metabolites were formed during food digestion (Figure 1).
The study was performed using pigs. Pigs are good animals to use to study the digestion of food because the pig gut strongly resembles the human gut. In our study, pigs were fed diets with either red and processed meat or white meat (chicken) for 4 weeks in a row. After 4 weeks, samples of the pigs’ gut content were collected and analyzed using metabolomics (Figure 2).
What Did Metabolomics Tell Us?
Using metabolomics, our group discovered that the type of meat affects the types and levels of gut metabolites. Different metabolites are formed after eating red and processed meat compared to after eating white meat . Some metabolites were less abundant in the pigs that ate the red and processed meat diet compared to those that ate the white meat diet, and other metabolites were more abundant. The metabolic differences we saw may be linked to differences in the composition of red/processed meat vs. chicken, but those differences may also be explained by changes in the digestive tract caused by these two types of meats, or changes in the helpful microorganisms that live in the digestive tract .
The pig study further revealed that a metabolite called carnitine as well as several metabolites created from the breakdown of carnitine were higher after the consumption of red and processed meat. We already knew that carnitine levels are higher in red meat than in white meat, so it was not surprising to find higher levels of both carnitine and its breakdown products in the gut following the consumption of red/processed meat. Other gut metabolites that were higher following diets containing red and processed meat were lysophosphatidylcholines, which are fat-breakdown products. This makes sense because the processed meats in the red and processed meat diets (ham sausage for example) contained more fat than the lean chicken meat in the white meat diets.
The End to This Quest: A Link With Colorectal Cancer?
Our quest in the gut, using metabolomics, provided some interesting discoveries. We found that there was a prominent difference in the types of metabolites detected after red and processed meat consumption in comparison to white meat consumption.
It was not possible to determine whether the pigs that ate a red and processed meat diet had a higher risk of developing colorectal cancer later in life because the study only lasted for 4 weeks. However, previous studies demonstrated that elevated levels of certain carnitine breakdown products, as well as lysophoshatidylcholines, are linked to the development of colorectal cancer. Levels of lysophoshatidylcholines are increased in colorectal tumor tissue , and elevated levels of carnitine metabolites can be found in the blood of colorectal cancer patients . Could it be that the carnitine metabolites and/or lysophoshatidylcholines are the missing link between red and processed meat consumption and colorectal cancer?
Ongoing and future scientific studies should focus on how carnitine metabolites and lysophoshatidylcholines might increase the risk of developing colorectal cancer. It could be that these metabolites attack the healthy cells in the gut, or maybe they provide nutrients for tumor cells.
Should We Eat Less Red and Processed Meat?
How should we apply this knowledge in our everyday lives? Based on what is known today about the health effects of red and processed meat consumption, recommendations  are to consume very little, if any, processed meat and to limit the consumption of red meat to no more than about three portions per week (equivalent to about 350–500 g cooked weight). This does not mean that you should completely avoid eating meat, since meat can be a valuable source of nutrients, including high-quality protein, iron, zinc, and vitamin B12. The results of future research may further finetune these guidelines, as scientists discover exactly how the metabolites generated from red/processed meats affect our bodies. We do not know the answers yet, so there are many more quests to come!
This work was funded by the Flanders Research Foundation (FWO) project G011615N. EV and TVH were supported as postdoctoral fellows by the FWO.
Metabolites: ↑ An intermediate or end product of metabolism.
Metabolism: ↑ The chemical reactions by which your body converts what you eat and drink into energy.
Colorectal Cancer: ↑ A form of cancer in the gut, with formation of dangerous tumors in the colon and/or rectum.
Colon: ↑ The longest part of the large intestine, connected to the small intestine at the one end and the rectum at the other.
Rectum: ↑ The last part of the large intestine, connected to the colon at the one end and the anus at the other.
Metabolomics: ↑ The study of all metabolites in a cell, tissue or organism.
Carnitine: ↑ A metabolite that plays an important role in the production of energy in cells.
Lysophosphati-dylcholines: ↑ Metabolites derived from fats.
Conflict of Interest
The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
 ↑ Goethals, S., Rombouts, C., Hemeryck, L. Y., van Meulebroek, L., van Hecke, T., Vossen, E., et al. 2020. Untargeted metabolomics to reveal red versus white meat–associated gut metabolites in a prudent and western dietary context. Mol. Nutrit. Food Res. 64:70. doi: 10.1002/mnfr.202000070
 ↑ Arnoldini, M., Lentsch, V., Latorre, D., Greter, G., Slack, E., Giorgetti, A., et al. 2021. How the gut microbiota influences our health and how we can influence it. Front. Young Minds 9:576428. doi: 10.3389/frym.2021.576428
 ↑ Pakiet, A., Kobiela, J., Stepnowski, P., Sledzinski, T., and Mika, A. 2019. Changes in lipids composition and metabolism in colorectal cancer: a review. Lipids Health Dis. 18:29. doi: 10.1186/s12944-019-0977-8
 ↑ Bae, S., Ulrich, C. M., Neuhouser, M. L., Malysheva, O., Bailey, L. B., Xiao, L., and et al 2017. Plasma choline metabolites and colorectal cancer risk in the women’s health initiative observational study. Cancer Res. 74:7442–52. doi: 10.1158/0008-5472.CAN-14-1835
 ↑ World Cancer Research Fund Cancer Prevention Recommendations: Limit Red and Processed Meat. Available online at: https://www.wcrf.org/dietandcancer/limit-red-and-processed-meat/ (accessed on March 4, 2021)