Early-life exposure to microbiota restricts colon cancer later in life.
It is known that the human gut contains trillions of bacteria, known as the microbiota, which play a crucial role in digesting food and regulating the immune system. Multiple studies show that certain bacteria and their metabolites are involved in triggering cancer, allowing it to develop, and/or making cancers treatment-resistant. However, the complex effects of prenatal and postnatal microbial exposure on adult health and disease outcomes remain unclear. Now, a study from researchers at Georgia State University shows that exposure to microbiota in the early stages of life plays a crucial role in inhibiting the development of colon cancer in adulthood. The team state that until now, the effects of prenatal and early postnatal microbial exposure on adult health and disease outcomes have received limited research. The study is published in the journal Cancer Immunology Research.
Previous studies have shown that gut microbiota are instrumental in promoting normal body function and a stable immune system in the host, however, the research has involved later stage life studies due to the difficulty studying microbiota in utero or in newborns. Humans are initially exposed to microbiota when they are born, either through delivery via the birth canal or Caesarean section; the mother has microbiota and metabolites which can affect fetal development. The current study investigates whether microbiota in this early period influences disease outcomes in adulthood.
The current study compares two groups of mice, the first group of mice were born to germ-free mothers and raised under germ-free conditions until weaning, after which they were transferred to normal conditions and exposed to normal microbiota. The second group of mice were born to normal mothers and then bred under regular conditions with microbiota; at six weeks old, all of the mice had colon cancer induced. Results show that the mice raised in the microbiota-free environment had much larger and many more tumors in the colon. Data findings show that the absence of microbiota in early life results in enhanced pro-inflammatory gene expression and an accumulation of immune cells called myeloid-derived suppressor cells, cells which suppress other immune cells which can help to limit or kill tumors.
The lab explain that myeloid-derived suppressor cells accumulate inside a tumor and suppress new, incoming immune cells that are trying to kill the tumor, which allows the tumor to grow bigger in size and increases numbers. One of the consequences of the absence of microbiota in early life, the group verified their results by blocking a specific pathway which helps to recruit myeloid-derived suppressor cells, and were able to completely reverse the enhanced size and number of tumors in ex-germ-free mice.
The team surmise that their findings highlight the crucial role of early life microbial exposure in establishing intestinal microbial homeostasis which is instrumental in restraining colon cancer in adulthood. For the future, the researchers state their results could provide insight into how the composition of microbiota in mothers and babies may control many inflammatory genes and susceptibility to diseases, including cancers, later in life.
Source: Georgia State University