SHORT ANSWERS TO THE BIG QUESTIONS

The gut microbiome is a complex community of microorganisms that interact with each other and with the host to modulate essential biological processes for our health. In the gut, about 10e14 of bacteria constitute up to 2 kg of microbial biomass, representing more than the number of human cells. Each individual carries on average nearly 200 species and each microbiome is unique. Bacterial phyla, such as Firmicutes, Bacteroidetes and Actinobacteria, are dominant with a relative abundance of 90%.

The symbiotic co-existence between humans and their respective gut microbiome is established at birth, is shaped during the first years of life and become stable towards adulthood. The gut microbiome benefits from a stable environment and a supply of nutrients provided in the intestinal tract. In return, gut microbiome microorganisms play a key role in various human physiological functions. They produce useful nutrients, stimulate our immune system and prevent pathogens from taking hold. The current thinking is actually that humans, like the majority of species on the planet, are "holobionts", an co-evolutive association between a superior organism (eukaryota) and its microbes.

Microbial diversity is a measure of the number of different species and, based on diversity indices, their even distribution in the community. We know today that a rich and diverse gut microbiome is essential to our health and is associated with resilience and maintenance of functional redundancy. On the contrary, a reduction of microbial diversity and richness in the gut leads to a state displaying instability of this community, which has impacts on our health. A low microbial diversity has been associated with short- and long-term health issues, such as bowel disease, allergies, diabetes, obesity, autism, colorectal cancer, and cirrhosis.

Western way of life (multiplication of caesarean section births, excess of antibiotics, low-fiber diet, pollutants...) leads to the decrease of our microbes diversity, that could lead to health risks. Today a fiber gap is recognized in western countries for both adults and children. This deficit impacts the microbiome structure, particularly through a decline in bacterial diversity. Some bacteria of the gut microbiome tend to disappear. Concomitant increase of inflammatory diseases and metabolic processes related to the gut microbiome suggests that these declining bacteria would be necessary for our health maintenance.

Diet plays an essential role for the modulation of the intestinal microbiota both in the short and long terms. Factors, such as a high fiber consumption or diversified diet, are correlated with greater diversity of the gut microbiome. One of the future challenge will be the development of personalized nutrition, taking into account the characteristics of the host gut microbiome at baseline and environmental factors to better explore microbiome  responses to interventional  diet.

The structure and composition of the gut microbiome is complex and once matured - 3 years old - prevents the proliferation of bacteria from the environment. This is known as a barrier function that benefits from a rich and diverse microbiome. Bacteria are swallowed every day, but they are transitive in our gut ecosystem: pathogenic bacteria are eliminated, or are carried in a healthy way.

Antibiotic therapy is a global treatment: even uses forskin infection or angina treatments, some transit through the intestine and destroys part of the gut microbiome bacteria, resulting in a richness and diversity loss and a barrier function weakening. Consequences: a pathogenic bacterium may take over and cause a disease. In adults, we know that antibiotic treatment, even a single dose, strongly disrupts the microbiome. But, except in the case of long or repeated antibiotic therapy, our microbiome is resilient: after 1 to 2 months, it has recovered its initial composition.

In case of pathology, our microbiome become unbalanced. For example, in cirrhosis (liver disease), where the stomach is less acidic and bile salts are less abundant, swallowed oral bacteria pass into the intestine without being stopped. The more severe the disease, the more the intestinal microbiome is altered. Major diagnostic tools to reveal the altered composition of the gut microbiome include gut microbiome profiling, transfer of healthy microbiome to a diseased host or new generation probiotics (bacteria) supplies for future treatments. These new medical approaches are being studied within our Homo symbiosus project, launched in 2019, with European funding of €2.5 million for 5 years. One of the greatest challenges in microbiome research will be to determine whether changes in the microbiome are responsible for any specific diseases, or whether these changes are consequence.

Metagenomic is a high throughput sequencing method used for the study of any microbial ecosystems, including the gut microbiome. Two sequencing technologies are currently used: 16S rDNA sequencing and whole shotgun metagenomics. Unlike 16S rDNA sequencing, which targets only a single gene, whole shotgun metagenomics, studies the entire metagenome – i.e. all genes of any microorganisms present in the sample. This sequencing technique provides a more precise picture at finer taxonomical ranks as for 16S rDNA sequencing. Shotgun metagenomic also offers the possibility to predictthe functionality of sequenced gene contents to draw hypothesis on the functional potentials of the gut microbiome.