Did you know? Our body is home to 100 trillion microorganisms, that's 10 times more bacteria than cells!
The microbiota encompasses all of these microorganisms. Today, teams at the Pasteur Institute in Lille are working on the links between the microbiota and metabolic diseases. Dr. Grangette's team is observing how changes in the composition of the microbiota occur in order to develop new therapeutic tools.
A complex ecosystem
The microbiota represents all the microorganisms present in our body. We often talk about the gut microbiota, but we also have an oropharyngeal, cutaneous, and vaginal microbiota. microbiota is very complex; until about fifteen years ago, researchers only had a very fragmented view of its composition.
Today, thanks to OMICs techniques, including new high-throughput sequencing technologies, researchers have realized that only a small part of its function was known. "That is to say, the tip of the iceberg; the entire submerged part remains to be discovered and understood." “Our bodies host approximately 100 trillion microorganisms,” explains Dr. Corinne Grangette, Research Director at the Lille Center for Infection and Immunity on the Pasteur Campus in Lille. “That’s 10 times more bacteria than our own cells. We are thus composed of 90% bacteria (by cell count). More than 1,000 different species are expressed across the entire population, and around fifty species are found in more than half of individuals. The first 1,000 days of our lives are crucial for our development.”
This period of developmental origins of health (DOHaD) extends from pregnancy (in utero) until the child is two years old. Within this context, the microbiota establishment window, which begins in the first few days after birth, also plays a significant role in the development of intestinal functions, particularly the immune system. The manner of birth (cesarean section, vaginal delivery), the child's diet (breast milk, formula, etc.), and the environment are all factors that can impact the composition of the microbiota and thus have a long-term influence. The mother's diet also has repercussions on the child's development, potentially influencing their metabolism.
Understanding the microbiota to take action
Each microbiota is unique. It is made up of large groups of bacteria, but its composition varies from one individual to another, a bit like a "genetic fingerprinting", Dr. Grangette emphasizes.
For the past 50 years, the incidence of chronic diseases (inflammatory bowel disease, obesity, diabetes, cancer, etc.) has been increasing, likely due to lifestyle changes and excessive hygiene. These chronic diseases are associated with changes in the composition of the gut microbiota and a decline in bacterial diversity: this is known as dysbiosis. The challenge, therefore, is to better understand these changes and gain a clearer understanding of the role of the microbiota in order to address them.
Today, research does not allow us to say whether changes in the microbiota cause pathology or whether pathology causes changes in the microbiota. "It's difficult to determine which came first, the chicken or the egg." Dr. Grangette comments. She explains that the imbalance can be transferable, for example if the microbiota of an obese donor is transferred into a sterile host, i.e. healthy, the pathology is transferred. "The exchanges are dynamic and most certainly take place in both directions, but the origins remain obscure for the time being." Genetic polymorphisms can, for example, influence the microbiota, which in turn influences the pathology; it is a two-way balance.
Researchers are now trying to target gut microbiota dysbiosis as a therapeutic tool. In the most extreme cases, a gut microbiota transplant can be performed, but the use of prebiotics (non-digestible fibers that promote the growth of certain gut bacteria) or probiotics (microorganisms with beneficial properties for the host) is currently experiencing a surge in popularity. Dr. Corinne Grangette's team is focusing on the study of these probiotic microorganisms.
A research team dedicated to probiotics
New avenues for development
Thanks to projects developed within the Transdisciplinary Research Center on Longevity, the team will initiate research on non-alcoholic fatty liver disease (NASH), in collaboration with a team from the Unit led by Professor Bart Staels at the Pasteur Institute in Lille. Since non-alcoholic fatty liver disease is a form of liver cirrhosis linked not to alcohol consumption, but to sugar consumption, this cirrhosis can progress to liver cancer. The researchers will focus on understanding the influence of probiotics on this condition, which affects 20% of French adults.
The team also works in partnership with INRA (National Institute for Agricultural Research) to study the functional properties of bacteria isolated from the human microbiota and capable of being cultured under satisfactory conditions (the majority being uncultivable). This collaboration opens up a new field of research: understanding the function of microbiota bacteria in order to use them as next-generation probiotics.
Dr. Grangette also wishes to develop a research area on the impact of perinatal colonization (DOHaD concept) by probiotic bacteria and to evaluate the impact in adulthood on the development of chronic diseases.
Gastronomic
The gut microbiota enhances chemotherapy
Recent work carried out by Dr. Mathias Chamaillard at the Pasteur Institute of Lille in conjunction with a team from Gustave Roussy has shown that two bacterial species present in the intestine can activate immune cells and boost the effectiveness of a frequently prescribed anticancer drug.
Their study identifies the role of Enteococcus hirae et Barenesiella intestinihominis These gut bacteria play a role in activating cancer-fighting T-cell immune responses. They enhance the effects of cyclophosphamide, a chemotherapy drug. Furthermore, the immune response boosted by these bacteria predicts longer progression-free survival in patients with advanced lung or ovarian cancer treated with chemoimmunotherapy. A prime example of a discovery that can lead to a better, longer life!
Microbiota and internal clock
The team led by Dr. Mathias Chamaillard has highlighted a crucial role for the interaction between the internal clock and the commensal microbiota, opening up promising perspectives in chronopharmacology. They demonstrated that an accumulation of bacteria, whose abundance fluctuates according to the circadian rhythm, correlates with alterations in the expression of numerous key players in the internal clock system. This, in turn, influences many vital processes in our body, such as anti-infective defenses, glucose metabolism, and the effectiveness of treatments. They also showed the importance of the composition of the gut microbiota on the anti-inflammatory and anti-proliferative properties of a chemical compound from the flavonoid family, widely present in fruits and vegetables, which is found to influence the internal clock.
