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The intestinal microbiota plays a role in many diseases, including infectious diseases, such as Clostridioides difficile infection, which is a bacterium that can develop in the colon when the intestinal microbiota is disrupted, most often after taking antibiotics. It also plays a role in inflammatory diseases, such as rheumatoid arthritis, in metabolic diseases, such as diabetes, in certain neuropsychiatric conditions, such as autism, and even in cancer. However, the "weight" of the microbiota compared to other factors, such as genetics or the environment, is often still unknown.

The diseases for which we are certain today that the microbiota plays a significant role are Clostridioides difficile infection, chronic inflammatory bowel diseases, metabolic syndrome, and Irritable Bowel Syndrome. It is important to keep in mind that the microbiota does not necessarily have a significant effect in all these diseases, and also not in all affected patients.

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Here's a quick look at how Prof. Sokol answers this question from his patients

To have a good microbiota, you must first avoid harming it and secondly, you must provide it with "good things". 

Antibiotics are well-known factors that alter the microbiota. However, it is important to remember that these medications are the ones that save the most lives on the planet. It is not about not taking antibiotics but taking them only when necessary. 

In our diet, consuming too much red meat, processed meats, and industrial products, known as "ultra-processed" products, promotes the proliferation of "bad" bacteria that have pro-inflammatory effects, meaning they will cause inappropriate activation of the immune system.

What stimulates the "good" bacteria in our gut are primarily plant fibers. Thus, you should consume plenty of fruits and vegetables in a diverse manner to nourish different bacteria and promote the diversity of the microbiota. Consuming fermented foods, such as yogurt, kefir, sauerkraut, or kimchi, could also be beneficial for our health and our microbiota.

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Here's a quick look at how Prof. Sokol answers this question from his patients
 

It is generally thought that bacteria are always harmful and sources of infections and other diseases.

But most often, and particularly in the case of the gut microbiota, this is not the case. Bacteria have colonized the digestive tract of animals since time immemorial, a relationship beneficial to both bacteria and animals has been established.
This is called "symbiosis."

In our digestive tract, bacteria enjoy free lodging and food! And in return, they help us stay healthy.

Thus, the microbiota fulfills many key roles, the main ones being:

• The digestion of fibers: plant fibers (such as inulin, for example, which is found notably in onions and leeks). Indeed, our human cells are incapable of digesting the fibers present in fruits and vegetables. After ingestion, they reach the colon where bacteria "digest" them for us. Bacteria extract what they need and produce in return very important molecules for the proper functioning of the digestive tract.
• The microbiota also produces vitamins, such as vitamin K, which is essential for proper blood clotting. 
• The microbiota plays a key role in educating our immune system. It helps to mature and develop the immune system, especially in young children. Intestinal bacteria help form and regulate innate and adaptive immune responses. 
• The microbiota plays a role in fighting pathogenic microorganisms, that is, harmful ones, which can cause intestinal infections.
• The microbiota also strengthens what is called the "intestinal barrier," that is, the proper "tightness" of the intestine. This prevents just anything from entering the body through the intestinal route.

There are indeed many other functions of the microbiota that are currently the subject of significant research.

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The dentist’s drill: the word alone is enough to make many of us break out in a cold sweat. And to make us fear a situation that is unfortunately commonplace in our society: 2 billion people suffer from cavities of their permanent teeth, and 514 million children suffer from cavities of their baby teeth. Even though oral diseases are largely preventable, they are very expensive for our healthcare systems. For this reason, researchers are actively seeking ways to counter them. Among the strategies is the oral microbiota.

In fact, our oral health could go hand-in-hand with the presence of certain oral bacteria: the friendly nitrate-reducing bacteria of the genera Neisseria and Haemophilus could ward off dental cavities and periodontal disease (sidenote: Periodontal disease Periodontal diseases affect the tissues that both surround and support the teeth. The disease is characterized by bleeding or swollen gums (gingivitis), pain and sometimes bad breath.  In its more severe form, the gum can come away from the tooth and supporting bone, causing teeth to become loose and sometimes fall out Explore WHO ) , while F. nucleatum is thought to be associated with periodontal disease, plaque and bad breath.

But when and how do these bacteria colonize our mouths and determine what happens to our teeth? Very early, seems to be the answer, from a Japanese study ¹ published at the end of 2024.

Brushing from the first tooth!

At 1 week of age, when the child is fed milk , the oral microbiota appears to be quite immature. But the situation soon changes: between 6 and 18 months, following the introduction of the first solid foods and the appearance of the first teeth, a baby's oral microbiota become comparable to that of an adult!

Most importantly, our bacterial allies—Neisseria and Haemophilus—and the dreaded Fusobacterium have already moved in. With a long-term lease: after the age of 36 months, a child's oral microbiota hardly evolves at all.

Thus, everything seems to come into play before the child's 3rd birthday, or even between 6 and 18 months: this short window of maturation of the oral microbiota seems to be essential for the future prevention of oral diseases such as cavities. And for our future dental bills!

Each year, during the World Antimicrobial Resistance Awareness Week, the WHO warns the public that the overuse of antibiotics promotes colonization of the gut by antibiotic-resistant pathogens. These pathogens include bacteria from the Enterobacteriaceae (sidenote: Enterobacteriaceae Enterobacteriaceae: family of gram-negative bacteria of the order Enterobacterales which includes the genera Escherichia and Klebsiella (two pathogens heavily implicated in antibiotic resistance), as well as Buttiauxella, Enterobacter, Gibbsiella, Salmonella, and Shigella, among others. Explore LPSN )  family, such as Escherichia coli and Klebsiella pneumoniae. These bacteria are responsible for severe infections, particularly in hospitals and among patients suffering from chronic inflammatory bowel diseases (IBD).

Now an alternative therapy is emerging in the fight against antibiotic resistance: commensal bacteria from the gut microbiota. Fecal microbiota transplantation appears to reduce the abundance of pathogenic Enterobacteriaceae, but the results have so far been mixed and have raised concerns about safety.

Hence the alternative presented in a study published in Nature ¹ : identify a combination of specific commensal bacteria capable of eliminating Enterobacteriaceae and determine their mode of action.

Winning combo of 18 strains

By analyzing stool samples from five healthy human donors, the researchers isolated 124 bacterial strains. Among the combinations tested, they identified a group of 18 synergistic strains, dubbed F18-mix, which significantly reduced the abundance of Klebsiella pneumoniae and Escherichia coli in germ-free mice (sidenote: Germ-free mice Germ-free mice: mice used in microbiota research that are bred in sterile environments and therefore free of microorganisms. They can be orally fed microbiota for studies under controlled conditions. ) .

F18-mix appears to specifically target Enterobacteriaceae without affecting other commensal bacteria, thus preserving the ecological balance in the gut while eliminating pathogens. 

The key to competition between F18-mix and Enterobacteriaceae appears to be access to carbon sources, and particularly gluconate. By depriving Enterobacteriaceae of this sugar essential to their growth, F18-mix gains the upper hand and prevents the former’s proliferation.

Towards a microbiotic therapy?

The researchers also tested the efficacy of F18-mix on a mouse model receiving microbiota from patients with Crohn’s disease or colitis. They observed not only a reduction in Enterobacteriaceae abundance, but also an increase in microbiota diversity. In colitis-susceptible mice, F18-mix even succeeded in reducing histological colitis scores and biomarkers of gut inflammation. 

This study paves the way for targeted microbiotic treatments against enterobacterial infections. Commensal flora may represent a promising alternative to antibiotics, limiting the emergence of resistance. However, these results came from controlled conditions in mouse models. Further studies will be required to demonstrate their applicability to humans.

Antibiotic-resistant gut infections due to prolonged antibiotic use or chronic inflammatory bowel diseases (IBD (sidenote: IBD Inflammatory bowel diseases are characterized by chronic inflammation of the gastrointestinal tract due to immune system dysregulation. They include Crohn’s disease and ulcerative colitis, which cause inflammatory flare-ups that can require hospitalization in 15% of cases. They have no cure. In 2019, 4.9 million people worldwide suffered from IBD Explore Inserm ) ) are an increasingly common threat, particularly in hospitals. The main culprits: pathogenic bacteria (sidenote: Pathogenic bacteria Bacteria that can cause infectious diseases. The WHO lists 15 families of antibiotic-resistant bacteria that currently pose a threat to human health, classified according to priority:
• Critical priority: includes Mycobacterium tuberculosis, which causes tuberculosis, and the Enterobacteriaceae family (including Escherichia coli and Klebsiella pneumoniae), the source of many hospital-acquired infections.
• High priority: includes other bacteria from the Enterobacteriaceae family, such as Salmonella typhi (typhoid) and Shigella (dysentery), whose resurgence is an issue in low-income countries, as well as Staphylococcus aureus, a major cause for concern in healthcare facilities.
• Medium priority: includes streptococci, which cause infections that pose particular danger to the vulnerable (newborns, the elderly). Explore ВООЗ )  of the digestive tract such as Escherichia coli or Klebsiella pneumoniae. Faced with this resistance, researchers are now exploring an unexpected avenue: using our gut’s “good” bacteria to eliminate the bad bacteria. They have recently identified a particularly effective group of these beneficial bacteria which may provide a natural alternative to antibiotics.

Winning cocktail: the power of good bacteria

Scientists developed a mixture of 18 strains of commensal bacteria (sidenote: Commensal bacteria Bacteria that cohabit peacefully with their host, particularly in the gut. They can benefit the host by boosting the immune system, aiding digestion, or fighting pathogens. ) , dubbed F18-mix, from gut microbiota samples taken from healthy individuals. The mixture was tested in mice and proved remarkably effective in reducing the abundance of Escherichia coli and Klebsiella pneumoniae in the gut, while preserving the gut’s good bacteria.

The secret? F18-mix bacteria eliminate pathogenic bacteria by competing with them to feed on certain sugars in the gut, such as gluconate. Gaining the upper hand, they deprive the harmful bacteria of their food source and prevent them from colonizing the gut.

Towards new microbiotic treatments? 

F18-mix does not just chase away antibiotic-resistant pathogenic bacteria: the researchers showed that, in mice suffering from inflammatory bowel diseases, such as ulcerative colitis or Crohn’s disease, it also helps alleviate clinical signs of the disease and calms inflammation.

While these results are encouraging, the research remains at the experimental stage. Since the tests were performed on mice, further studies will be required to confirm the efficacy of the treatment in humans. Nevertheless, resistant bacteria should take note: our microbiota could well change the rules of the game, revolutionizing the treatments of tomorrow.

The digestive tract is the main replication site of the human immunodeficiency virus (HIV), which is the cause of AIDS. The presence of HIV is associated with inflammation of the gut mucosa and an imbalance in the bacteria of the microbiota (dysbiosis (sidenote: Dysbiosis Generally defined as an alteration in the composition and function of the microbiota caused by a combination of environmental and individual-specific factors. Levy M, Kolodziejczyk AA, Thaiss CA, et al. Dysbiosis and the immune system. Nat Rev Immunol. 2017;17(4):219-232.   ) ), which could influence progression of the disease.

Not only bacteria in the microbiota... 

But what about the viruses which are present alongside bacteria, fungi, and archaea in the gut microbiota? Are they, like bacteria, involved in disease?

To answer this question, a team of Mexican researchers analyzed the ‘virome’ (viral component of the microbiota) in the feces of 92 HIV-positive individuals at different stages of infection but not receiving treatment and compared it with that of 53 healthy individuals. ¹

From the HIV-positive individuals, they then selected 14 people suffering from immunodeficiency, i.e. a low level of CD4 T cells, the cells in which HIV multiplies. 

They took stool and blood samples from them before antiretroviral treatment and at four timepoints during antiretroviral treatment. Their aim was to study changes in immunity and the gut microbiota during the first two years of therapy.

A striking expansion of certain virus species

They found that in those most affected by the disease, i.e. those suffering from severe immunodeficiency (CD4 T cell count < 350), three species of virus are present in great abundance in the microbiota: Anelloviridae (anelloviruses), Adenoviridae, and Papillomaviridae. Anelloviruses appear to be particularly affected by antiretroviral treatment, their markers decreasing significantly after 24 months of treatment. 

One notable finding was that the presence of anelloviruses at the start of treatment is associated with a poorer recovery of immunity and a lower CD4 T cell count, and therefore less effective treatment.

For the scientists, this study represents an important step forward. Not only does it provide a better understanding of the virome, a component of the gut microbiota little studied and less well understood than the bacterial component; it also provides a better understanding of the involvement of microbiota viruses in HIV infection.

Towards better monitoring of patients

These results open up the prospect of one day being able to use anelloviruses as a marker to predict the effectiveness of treatment and monitor the immune recovery of those affected by HIV. This is good news, since the fight against AIDS remains a major public health concern.

Extreme depletion of CD4 T cells, inflammation, bacterial dysbiosis, disruption of the epithelial barrier, microbial translocation... HIV’s impact on the gastrointestinal tract is now well documented. 

While no research has yet succeeded in defining a bacterial dysbiosis signature associated with HIV, we do know that enteropathy is involved in the chronic activation of the infection and in the development of immunodeficiency. 

Better understanding the role viruses play in the gut microbiota during HIV infection

The viral component of the gut microbiota is less well known than the bacterial component. To what extent does it play a part in this process? To find out, scientists in Mexico City investigated whether our ‘virome’ is associated with HIV infection and immunodeficiency. ¹

They began by comparing the CD4 T cell count and gut bacteriome and virome (viral RNA and DNA) of 92 untreated HIV-positive individuals with those of 52 healthy individuals at risk. 

To better understand the association between gut microbiota composition, HIV-related immunodeficiency, and immune recovery, they followed 14 HIV-positive individuals receiving antiretroviral therapy (ART) for two years. Blood and stool samples were taken at baseline (before ART) and at 2, 6, 12, and 24 months after the start of treatment.  

The results showed that HIV-positive individuals do indeed have reduced alpha bacterial diversity, with an increase in Enterococcus, Streptococcus, and Coprococcus in those at an advanced stage of infection. However, no clear signature could be identified.

Marked expansion of certain viruses

Compared with HIV-seronegative volunteers, individuals suffering from severe immunodeficiency (CD4 count < 350) showed radical changes in the composition of their gut virome:

• Increase in sequences of Anelloviridae (anelloviruses), Adenoviridae, and Papillomaviridae
• Decrease in plant viruses of the Tobamovirus genus

No Anelloviridae were detected in HIV-seronegative individuals.

The researchers believe that this expansion of viruses could contribute to the pathogenesis of AIDS by damaging the gut barrier and promoting inflammation.

The data also showed a striking link between HIV-associated immunodeficiency and the detection of Anelloviridae sequences, which were completely absent in the 53 HIV-negative individuals. In highly immunocompromised individuals, the abundance of anelloviruses decreased progressively during ART. 

A predictive tool?

Another finding: the detection of anelloviruses prior to treatment independently predicts poor immune recovery.

Despite the limitations of this study (majority of subjects male, dietary factors not taken into account, etc.), it suggests that the detection of anellovirus sequences in stool could be used to predict and monitor immune recovery during ART. 

Another step forward in our understanding of the gut microbiota, but above all a small step forward in the fight against HIV, a virus which, according to the WHO, affected 39 million people and caused 630,000 deaths in 2023. ²

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