Non-alcoholic steatohepatitis (NASH) is thought to affect 24% of the world’s population and an alteration of the gut microbiota has been implicated in the progression from advanced fibrosis to cirrhosis. The stool microbiota of 163 US subjects was analyzed to determine the diagnostic capacity of this link. The participants included 54 non-NASH control subjects, 27 NASH patients suffering from cirrhosis (the most advanced stage of the disease) and their first-degree relatives. The results were supported by data from two independent Chinese and Italian cohorts.

Two independent signatures

The results showed a loss of bacterial diversity in the NASH-cirrhosis patients. This was found to be correlated with certain clinical parameters, notably LDL levels, coagulation, and blood insulin levels. More importantly, a machine learning (sidenote: Machine Learning Automatic learning whereby artificial intelligence solves a task based on metagenomic and metabolomic data collected, in this case the identification of discriminating bacterial species. Wazid M, Das AK, Chamola V, et al. Uniting cyber security and machine learning: Advantages, challenges and future research. ICT Express, 2022; 8(3), 313-321. ) approach identified a bacterial signature for cirrhosis based on 19 species with a diagnostic accuracy of 0.91. This dysbiosis was associated with a functional signature, notably the biosynthesis of specific amino acids (aromatic and branched), fatty acids and nucleotides. These results, which were confirmed in independent cohorts, suggest that the dysregulation of essential microbial metabolic processes may contribute to the progression of the disease to cirrhosis. Therefore, altered metabolite production may explain how gut dysbiosis can affect the liver. To further support this potential causal link, an independent signature based on 17 metabolites was identified, which provided the same diagnostic accuracy as the microbial signature. Significant correlations were found between the two signatures.

Distinguishing cirrhosis from fibrosis

The researchers subsequently sought to refine this microbial signature. By also considering age and blood albumin levels, they slightly improved the signature’s precision in distinguishing cirrhosis patients from control subjects, and above all validated its effectiveness in the Chinese and Italian cohorts. Lastly, the inclusion of a highly discriminating additional parameter (increased levels of aspartate aminotransferase (AST) in the blood of cirrhosis patients) has made it possible to distinguish cirrhosis from early-stage mild to moderate fibrosis.

A non-invasive diagnostic tool or even a treatment?

The robustness of this intestinal signature across geographically and culturally distinct populations shows its potential as a diagnostic tool for cirrhosis. Some bacterial species in the gut microbiota may become a useful non-invasive and universal diagnostic tool, or even potential targets for new therapeutic approaches.

Introduction

Though a more rational use of antibiotics has long been overdue, we must not lose sight of the fact that over the course of the last 80 years their widespread use has saved many millions of lives. They have served as our principal weapon in the fight against bacterial infections. Alongside vaccinations, they have added around 20 years to the average life.¹

FROM THE ANTIBIOTIC ERA TO THE MICROBIOTA ERA

Unfortunately, antibiotics eliminate not only pathogenic bacteria, but commensal ones too.² The intestinal microbiota is affected, and likewise all the other human microbiota (cutaneous, lung, urogenital...) that protect against pathogen overgrowth. While it remains difficult to define a healthy microbiota with any precision or to provide an adequate description of dysbiosis, science is beginning to understand the ways in which antibiotics affect the functioning of these ecosystems and likewise the consequences of such changes for health over the short and long term³ (See Figure 1).

ANTIMICROBIAL RESISTANCE, A GLOBAL PUBLIC HEALTH PROBLEM

Because of the widespread overuse and misuse of antibiotics in humans and animals, bacteria causing both benign and life-threatening infections are becoming increasingly resistant to them. In 2015, antibiotic-resistant pathogens were estimated to be causing over 50,000 deaths each year in Europe and the United States.³ “Antibiotic resistance is one of the biggest threats to global health, food security and development today” states the WHO.

More and more evidence has come to signal Fusobacterium as an important intestinal bacterial pathogen associated with colorectal cancer. However, prior to a recent retrospective study, the bacterium’s role in locally advanced rectal cancer as well as its fate following chemotherapy and its involvement in tumor progression, all remained unknown. This study measured levels of F. nucleatum in the tumor microenvironment of 143 patients prior to the excision of their tumor: 87 of these patients were treated with neoadjuvant radiochemotherapy prior to excision, while the remaining 56 were control subjects.

Lower abundance of F. nucleatum with pre-operative chemotherapy

Visualization and quantification of F. nucleatum using in situ hybridization showed that the bacterium was mainly found on the luminal surface of the tumor and that radiochemotherapy significantly reduced its frequency. The density of F. nucleatum was significantly higher in untreated tumors than in treated tumors (median score of 7.4 versus 1.6), while 58% of tumors tested positive for F. nucleatum in control patients, compared to only 26% in chemotherapy patients.

Abundance is not harmful, but persistence signals relapse

The effects of treatment were evaluated using paired samples (taken before and after radiochemotherapy) from 71 patients. F. nucleatum abundance was not predictive of response to treatment. However, persistence of the bacterium following radiochemotherapy increased the risk of relapse by a factor of nine. Although no causal relationship has been confirmed, this may be due to a lack of immune cytotoxicity activation: tumors that became F. nucleatum-negative following treatment showed a strong increase in CD8+ T cells, whereas tumors that remained F. nucleatum-positive showed no induction of CD8+ T cells in post-treatment samples.

Persistence of F. nucleatum, a future biomarker?

Therefore, the persistence of F. nucleatum following chemotherapy may be associated with high relapse rates in locally advanced rectal cancer, a finding potentially related to the suppression of immune cytotoxicity. This promising biomarker for predicting the risk of relapse following neoadjuvant radiochemotherapy may lead to a more personalized clinical management of rectal cancer.

Defined as the inability to conceive offspring despite frequent sexual intercourse over at least a year, infertility affects 8% to 12% of couples of childbearing age. While IVF has quickly emerged as the most effective treatment, some women fail to become pregnant due to recurrent implantation failure (RIF). Hormonal, vascular, or immune disorders have recently been blamed, but such disorders cannot explain all embryo implantation failures. Already linked to numerous gynecological diseases and pregnancy-related disorders, might imbalances in the vaginal microbiota be involved in IVF failure as well?

An unbalanced, lactobacilli-depleted microbiota

To test this hypothesis, the vaginal microbiota of 67 women who had previously attempted IVF was analyzed. Of these, 27 had experienced unexplained RIF and 40 had carried their pregnancy to term following a single treatment cycle. The results showed the women who had experienced an RIF to be suffering from vaginal dysbiosis, specifically a more diverse and abundant microbial flora, with more bacteria linked to various genital infections (bacterial vaginosis, vaginitis, urinary tract infections). Conversely, their vaginal microbiota was relatively less rich in lactobacilli. According to the authors, the pregnancy rate exceeded 72% where lactobacilli made up more than 90% of the vaginal microbiota and fell to 34% where this was not the case.

Will the risk of IVF failure soon be predictable?

Lastly, the RIF patients also had different levels of certain substances produced by the vaginal microbiota, in particular significantly fewer of the molecules necessary for the implantation and development of the embryo, with this scarcity directly correlated to the reduced abundance of lactobacilli. The authors believe that the composition of the vaginal microbiota, and particularly lactobacilli depletion, plays a key role in the recurrent embryo implantation failure. They hope these results will pave the way for the development of biomarkers capable of predicting the risk of RIF.

Most people contract a respiratory syncytial virus (RSV) infection before the age of one. While symptoms are limited to a mild upper respiratory tract infection in most infants, 0.5%–2% of them develop a severe infection of the lower respiratory tract, such as bronchiolitis or pneumonia, requiring hospitalization. There is currently no vaccine or other preventive treatment for RSV.

Phylogenetic clusters

With the links between the intestinal microbiota and respiratory health becoming increasingly clear, a research team compared the microbiota of 37 healthy infants to that of 58 hospitalized infants with confirmed moderate or severe RSV infection. A fecal analysis using 16S RNA sequencing showed no significant differences in microbial diversity (alpha) among the three groups. However, the analysis did reveal phylogenetic clusters able to discriminate not only RSV infants from the control subjects, but also the 53 moderate cases from the 5 severe cases. In particular, when compared to the control subjects, infants with severe RSV infection showed an increased abundance of the S24-7 bacterial family in their gut microbiota, whereas bacteria from Moraxellaceae, Tissierella and Soehngenia families were found to be reduced

S24-7: a severity marker?

Within the S24-7 family, OTU (sidenote: Operational Taxonomic Unit groups of organisms usually not cultivated or not identified, classified on the basis of the similarity of the DNA sequencing of a given gene. Frequently used as an equivalent to the concept of species )  191 was of particular interest to the researchers, since it was more abundant in the severe cases than in either the control subjects or moderate cases. OUT 191 may therefore be an indicator of the severity of the disease. The hypothetic mechanism of action could be a potential interaction with the immune system. S24-7 bacteria carry genes that code for enzymes that degrade IgA, an immunoglobulin involved in the protection of mucous membranes and the prevention of upper respiratory tract infections. However, available data do not reveal whether S24-7 bacteria are the cause or the result of RSV infection, especially since IgA degradation or a modification of immune responses may be caused by other metabolites in the microbiota that are not associated with S24-7 bacteria. In any case, this study lays the groundwork for identifying microbial clusters associated with RSV infection and its severity. It may help identify infants at risk of developing severe RSV infection and lead to the development of immunoprotective microbial mixes.

Although relatively stable, the composition of the intestinal microbiota can evolve, favorably or unfavorably, due to multiple factors (diet, environment, health status, medication, etc.), with an impact on the metabolism. Studies have already shown the beneficial effects of physical exercise on its composition and diversity. But what about the intensive training of professional athletes? A team of Polish researchers tried to answer this question, comparing the microbiota of 14 marathon runners and 11 cross-country skiers with that of 46 sedentary subjects. Their objective was to determine whether there is any link between training level and bacterial composition.

A richer and more diversified microbiota

The intestinal microbiota of the high-performance athletes was richer and more diversified overall, ensuring better resistance to various diseases. This was all the more so when their diet was high-calorie and rich in nutrients (especially zinc and copper). As heavy consumers of vegetables and starchy foods, the professional athletes harbored more of the bacteria involved in breaking down fiber in their digestive tracts.

An influence on athletic performance?

Their microbiota was also richer in bacteria belonging to the large Firmicutes family and poorer in Bacteroidetes. According to a recent study, a high F/B ratio is associated with high oxygen consumption (VO2 max), which is essential to high-level athletes. Prevotella bacteria were also abundant in the athletes. They are associated with enhanced physical performance and were particularly common in the marathon runners. Another difference was the increased production, in the athletes, of certain molecules thought to improve degradation of sugars and fats and to enhance performance during strenuous exercise. So, does the level of training influence the composition of the microbiota? For the authors, the former shapes the latter, and the latter, in turn, contributes to the level of athletic performance.

From its early days, metagenomic research has sought to understand the links between the gut microbiota and obesity. Since 2012, MetaCardis (sidenote: European project involving over 2,000 participants in good health or at different stages of progression of cardiometabolic diseases (obesity, diabetes mellitus and cardiovascular disease). The participants were recruited in Paris (France), Leipzig (Germany) and Copenhagen (Denmark). www.metacardis.net )  has been studying the potential role of microbiota in the development of cardiometabolic diseases. Its work includes the characterization of the microbiota of 888 obese and non-obese subjects, more than 42% of whom reported taking at least one type of medication. The effects of the most common therapies were assessed, particularly those of statins.

An enterotype marker for inflammation?

Several links were found between obesity markers and gut microbiota in the 782 participants not taking statins. For example, stool softness and inflammation increased with body mass index (BMI), while BMI, body fat percentage and serum triglyceride levels were correlated with changes in the gut microbiota. Most importantly, a link was observed between the prevalence of Bact2 enterotype (high proportion of Bacteroides, low proportion of Faecalibacterium), BMI and inflammation. Thus, while only 3.90% of normal weight and overweight people had this enterotype, this percentage rose to 17.73% in obese individuals. Moreover, the greater the number of Bacteroides, the more acute the inflammation, including among slim people. In addition, the inflammation levels of participants with the Bact2 enterotype were higher than expected based on their obesity status alone, which suggests Bact2 is a potentially dysbiotic enterotype associated with low-grade inflammation.

Effect of statins on microbiota

Conversely, among the 106 participants receiving statins, the prevalence of Bact2 did not increase with BMI: among obese subjects, only 5.88% of those treated with statins had the Bact2 enterotype (vs. 17.73% of obese subjects not treated with statins). This result–confirmed on two separate cohorts–suggests that statins may limit alterations to the intestinal microbiota. Although the study did not establish a causal link between the drug and the lower prevalence of Bact2, two processes, or a combination thereof, may be involved:

• By influencing the growth of certain microorganisms, statins may counteract the role of gut bacteria in patients with inflammatory and metabolic obesity comorbidities

• And/or the anti-inflammatory effects of statins may attenuate the microbiota-host interactions and allow the subsequent development of enterotypes not associated with inflammation

New projects will be launched to verify whether statins have a direct effect on the bacterial flora or whether other factors (such as an improved lifestyle for people with higher awareness of cardiovascular risk) are involved.

We now know that our diet shapes the composition of our microbiota and, therefore, our health. While many studies have shown good eating habits to have a positive influence on the composition of the gut microbiota, few have explored the relationship between eating habits and salivary microbiota. Since food enters the body via the mouth, does the composition of the salivary microbiota reflect our eating habits and, accordingly, our health status?

Teenagers’ eating behavior under the microscope

To find out, the authors analyzed the salivary microbiota of 842 healthy Finnish teenagers. The teenagers completed a questionnaire aimed at determining their eating habits and were classified according to whether they avoided fruits and vegetables (no FV diet) (42.9%), had healthy meals (45.5%) or junk food (11.6%) and regularly had breakfast (83.1%) and dinner (82.4%).

Show me your salivary microbiota and I will tell you how you eat

Surprisingly, the teenagers’ salivary microbiota remained similar both in terms of diversity and composition whatever their food preferences (no FV diet, healthy meals, or junk food). On the contrary, the regularity of meals did influence diversity. Teenagers with a regular diet had greater microbial diversity than those who skipped meals. Consequently, “irregular eaters” are likely to show reduced diversity, with a diverse microbiota generally considered beneficial to health.

Increase in bacterial content associated with poor eating habits?

The study also showed an abundance of certain bacteria in the saliva of teenagers with a no FV diet and of those skipping meals. The presence of these bacteria in the saliva has previously been associated with oral disease and poor oral hygiene. The authors believe that meal regularity is more important to the composition of the salivary microbiota than diet, and that some salivary bacteria may serve as an indicator of poor eating habits.

Over the course of our lives, we consume around 60 tons of food. ¹ To ensure proper digestion, this food takes a long trip through our digestive tract, which measures roughly 5 meters from mouth to anus. ² The purpose of this trip is to break the food down into tiny pieces that can be absorbed by the body to provide it with all the necessary nutrients—the small building blocks that power our muscles, fuel our brain, maintain our bones, and much more.

To facilitate absorption, our digestive system is not only very long, but it also has a very large surface area, thanks to numerous folds (much like corrugated cardboard). Laid out flat on the ground, the surface area of the digestive tract’s walls would cover between 32 m2 (roughly half the size of a badminton court) ² and 250-400 m2 (similar to that of a tennis court). ¹ 

Throughout its journey, the food being digested encounters the trillions of gut flora microorganisms inhabiting the space between the lumen of the digestive tract and the protective mucus lining the digestive tract walls. The size and composition of the microbiota vary according to the parts of the digestive tract, with the number of microorganisms increasing from the stomach to the anus. There are estimated to be ³: 

• fewer than 1,000 bacteria/mL in the stomach, an environment too acidic for many species; 
• millions of bacteria/mL in the small intestine, an acid- and oxygen-rich environment where transit is rapid. Here, bacteria adapted to these conditions (e.g., Lactobacillaceae) predominate, growing rapidly and capable of attaching to the walls; 
• billions of bacteria per gram of digestive contents in the colon, where bacteria capable of fermenting undigested fiber (e.g., Prevotellaceae) live in an oxygen-free environment. 

These microorganisms help us to survive (protecting us from pathogens, regulating our immune system, etc.) ¹, but also help us to digest our food. For example, we are unable to digest dietary fiber, which thus arrives intact in the colon. There it encounters bacteria which, unlike us, are able to digest it, i.e., to use it as a substrate for their own metabolism, and to convert it, in particular, into short-chain fatty acids.
Our gut flora also provides us with essential nutrients, such as vitamins B12 or K, for example. ¹  

Our food isn’t sterile, and that’s a good thing. When we bite into an apple, a tomato, or any other fresh fruit or vegetable, we enrich our gut microbiota with bacteria and other microorganisms. Thus, biting into an apple introduces microorganisms beneficial to our health (bacteria, viruses, fungi), which temporarily colonize and enrich our gut microbiota. ⁵

Fermented foods, a source of good bacteria

Fermented foods are another source of bacteria and yeast. These foods include cheese, yogurt, kefir, and other fermented milk products, as well as fermented vegetables like sauerkraut, to mention just a few. If the foods are neither cooked nor pasteurized, the bacteria and yeasts stay alive, and can alter the composition of our gut microbiota, either temporarily (increasing immediately after consumption and then gradually decreasing), or even long-term, if the food is consumed regularly. ⁶

Because they are alive, the bacteria produce a wide variety of metabolites also found in the fermented foods in our diet, including: 

• organic acids (lactic acid in yogurt or pickles),
• bioactive peptides (bacteriocins in sauerkraut that inhibit competing pathogenic bacteria)
• and vitamins (vitamin K in nattō, i.e., Japanese fermented soybeans).

These bacterial metabolites can improve the functioning of our gut microbiota (strengthening the intestinal barrier, modulating inflammation, etc.), support our immune system, and provide health benefits for the host. ^6,7

Fermented Foods

Water also enriches our microbiota

Let’s not forget another major dietary source of microorganisms: what we drink. Bottled, tap, filtered, or well water: not all water is the same when it comes to chemical, mineral, and microbial composition, or the effect on our microbiota.

Do you mainly drink well water, which naturally contains more diverse microbial communities? If you do, your gut microbiota is likely to be more diverse than it would be if you drank tap, filtered, or bottled water. ⁸

Fiber to nourish our gut microbiota 

But food isn’t just a source of bacteria. It’s also a source of nutrients that feed these microorganisms. Foremost among these nutrients are the famous dietary fibers—carbohydrates our body can’t digest, but which our gut microbiota relishes. Resistant to digestion, dietary fibers eventually reach our large intestine, where they feed our bacteria. They come in a wide variety ⁹ and include :

• fermentable dietary fibers such as inulin (found in chicory or Jerusalem artichokes),
• pectin (apples, lemon peel),
• and galactooligosaccharides (breast milk, legumes),
• as well as non-fermentable fibers, such as resistant starch in grains. 

The fermentation of fermentable fibers by bacteria produces metabolites, including short-chain fatty acids (SCFAs) such as butyrate, which has remarkable properties:

• beneficial effects on the microbial community (e.g., inhibition of pathogens);
• improvement of gut barrier function (stimulation of proteins that help tighten the cells of the gut wall, thereby reducing gut permeability; stimulation of protective mucus production);
• and direct metabolic (e.g., on satiety) and immunological effects on the host. ¹⁰

Probiotics, prebiotics, and postbiotics to rebalance the microbiota  

If your diet is no longer adequate or rebalancing is necessary (e.g., following antibiotic treatment), your healthcare professional may give your microbiota a little boost by prescribing: 

• probiotic capsules containing live microorganisms beneficial to your health. Probiotics have different modes of action depending on the strain, and no specific beneficial effect can be generalized from one strain to another. 
• and/or prebiotics, which specifically “feed” certain beneficial microorganisms in the gut microbiota. Prebiotics are equivalent to dietary fibers. 
• and/or postbiotics, which include the beneficial small molecules produced by probiotics (such as SCFAs), as well as dead probiotics and their fragments. 

Since our diet also nourishes our gut microbiota, it plays a key role in gut microbiota composition. ^1,11 The more you feed bacteria the foods they like and know how to make use of, the more they proliferate at the expense of other microorganisms. There may also be cooperative relationships between bacteria, with the molecules produced by some serving as food for others. ¹

Much like a fingerprint, each individual harbors within their gut a specific combination of a few hundred bacterial species from among the approximately 3,000 species identified in the human digestive system to date. ^12,13

This microbiota is the result of years of development and rebalancing, beginning at birth, in which diet plays an essential role:

• breastfed infants develop a wide range of Bifidobacterium spp. strains beneficial to their digestion and health,
• whereas infants fed formula have a different, more diverse flora,
• and undernourished infants have an immature, imbalanced (dysbiotic) gut microbiota that harbors more pathogens. ^1,12,13

How is this possible? Breast milk, the gold standard for infant nutrition, contains not only microorganisms beneficial to the child’s health but also—and most importantly—prebiotics. These prebiotics, known as oligosaccharides, aren’t digested by the baby, but instead nourish and promote the growth of beneficial bifidobacteria. ^13,14  They thus shape the baby’s gut microbiota, with lifelong implications for health (immunity, etc.). ¹⁴

A different gut microbiota at every stage of life 

The microbiota continues to develop during early childhood.

• Between 4 months and 1 year of age, dietary diversification goes hand in hand with the arrival and establishment—or otherwise—of new microorganisms, and the decrease of others. African children who consume diets rich in fiber and starch have a more diverse microbiota which produces beneficial fatty acids, whereas Western diets low in fiber reduce diversity and levels of these protective fatty acids. ¹
• Between the ages of 1 and 3, the composition of this community continues to diversify.
• By ages 3 to 5, a child’s gut microbiota isn’t yet fully comparable to that of an adult, but begins to resemble it closely. ^12,15  
• In adulthood, our gut microbiota is diverse and is generally dominated by Firmicutes and Bacteroidetes.  
• Starting at age 70, gut microbiota composition can be affected by biological changes (e.g., poorer digestion), as well as changes in dietary habits, which are often less diverse. The result is a decline in gut microbiota diversity, including a decrease in bacteria such as the beneficial Bifidobacterium spp. ¹²

Skin, lungs, and vagina also influenced by diet 

However, it would be wrong to think that our diet only affects our gut microbiota. Through the gut flora, it may influence other microbiomes as well. Take, for example, our skin microbiota, with various common skin conditions, such as acne, atopic dermatitis, psoriasis, and rosacea, having been linked to gut dysbiosis. ^16,17  

In the case of acne ^17,18: 

• a diet high in sugar, common among adolescents in developed countries, may lead to an imbalance in the gut flora;  
• disrupted gut bacteria may produce molecules capable of entering the bloodstream, reaching the skin, and altering various skin functions (inflammation, cell proliferation, lipid metabolism, etc.), thereby indirectly causing dysbiosis of our skin microbiota; 
• this skin microbiota imbalance may result in an overproduction of sebum, oil, and skin cells, thereby promoting the development of acne.  

This appears to be a two-way process, with acne in turn affecting the composition of the gut microbiota. This may result in a vicious cycle. ¹⁸ Thus, the gut and the skin are closely linked via a communication channel known as the gut-skin axis. ¹⁷ 

The same is true of the lung microbiota, which is part of a two-way gut-lung axis:  

• the gut microbiota may contribute to lung diseases, with gut dysbiosis often going hand in hand with winter respiratory infections ¹⁹ or asthma ²⁰;  
• conversely, lung conditions may influence the composition of the gut microbiota. ¹⁹

Diet may also influence the urinary microbiota, with gut dysbiosis potentially increasing susceptibility to urinary tract infections, although some findings in this area appear contradictory. ²¹

The same is true for the vaginal microbiota: reduced consumption of alcohol and animal proteins, and a higher intake of linolenic acid—typical of plant-based foods—can have a beneficial impact on the vaginal environment by maintaining a microbiota where protective Lactobacilli predominate. ²²

In both these cases, the interactions between microbiota are most likely linked to the proximity of the anus (gut microbiota), the vaginal opening (vaginal microbiota), and the urethral opening (urinary microbiota), such that bacteria of intestinal origin have little distance to travel to colonize the vagina or bladder. 

Thus, diet is clearly one of the most powerful levers for changing the composition and activity of the gut microbiota. Broadly speaking, a plant-based diet rich in fiber promotes protective bacteria, whereas a diet high in sugars, animal proteins, and saturated fats leads to a more inflammatory profile. ^16,23,24

Nutrients

Mediterranean diet: the gut microbiota’s friend 

Therefore, a plant-based diet, or the famous Mediterranean diet (which prioritizes fruit, vegetables, seeds, legumes, fish, nuts, and olive oil, while limiting sugar and meat), are healthy choices.

Scientific research seems to confirm this: a study conducted over the course of a year examined the effects of a Mediterranean diet on older adults in the United Kingdom, France, the Netherlands, Italy, and Poland. The study found a change in their gut microbiota, with an increase in bacteria associated with reduced frailty, improved cognitive function, and lower inflammation. ²⁵

Which beverages are beneficial to the gut microbiota? 

When it comes to beverages, the polyphenols in wine (part of the Mediterranean diet) ²⁶ and tea ²⁷ are also associated with a more diverse and healthier microbiome.

On the other hand, having a taste for sugary drinks (especially if consumption exceeds two glasses per day) has serious consequences for the gut microbiota: regular consumption appears to deplete populations of various beneficial bacteria, such as Bacteroides pectinophilus. This bacteria feeds on pectin but can’t process the sugars in soda, and thus its population declines when sugary drinks are consumed. ²⁸ 

Diseases linked to poor diet 

As seen previously, the gut microbiota varies greatly from one person to another depending on age, lifestyle, diet, etc. These variations are normal and can help the body adapt to its environment. But at times, the gut flora undergoes profound changes, which can be the cause and/or consequence of health problems. ^12,30

Various intestinal conditions ^12,30 appear to be linked to dysbiosis:  

• in irritable bowel syndrome (IBS), the loss of microbial diversity is thought to weaken the functions of the epithelial barrier and to alter the inflammatory response, which explains in part the symptoms of this condition. 
• in inflammatory bowel disease (IBD), even though a direct causal link has not been proven, microbial imbalances (particularly a decrease in butyrate-producing bacteria) are thought to contribute to the severity of the disease. 
• in celiac disease, dysbiosis appears to create an inflammatory environment and may prevent the intestinal mucus layer from protecting against the invasion of harmful antigens and pathogens. 
• in colorectal cancer, a reduction in beneficial butyrate-producing bacteria and an increase in opportunistic pathogens may contribute to tumor development. 

Gut dysbiosis is also implicated in numerous metabolic disorders: ^12,30,31,32

• in the case of obesity, gut dysbiosis increases the body’s ability to extract energy from food, promoting fat storage and inflammation. 
• in the case of type 2 diabetes, patients exhibit an increase in Betaproteobacteria (associated with elevated blood sugar) and a decrease in beneficial butyrate-producing bacteria such as Roseburia spp. 

The gut-brain axis is also affected: ¹²

• in Alzheimer’s and Parkinson’s diseases, a dysbiosis (e.g., an increase in Escherichia/Shigella for Alzheimer’s) appears to be associated with a peripheral inflammatory state that may contribute to these conditions. 

Adopting healthy habits for your microbiota  

While diet is one of the most powerful ways to influence our gut microbiota, it is by no means the only way. Exercise, when practiced in moderation (at less than 50% of VO2max), facilitates intestinal transit, improves the quality of the mucosa lining the digestive tract’s walls, and boosts our gut microbiota by promoting the establishment of a rich and beneficial flora. ³³ 

As with everything, perfect is the enemy of good: sixty minutes of high-intensity endurance training (at 70% of VO2max) can lead to abdominal pain, nausea, and diarrhea. ³³ And in case you need further convincing, 30% to 50% of athletes suffer from digestive problems, which rises to 90% for those who take part in ultra-endurance events. ³⁴

Lastly, good habits also require us to be mindful of our environment in the broadest sense of the term.
Or more precisely, to be mindful of the exposome—the set of environmental factors to which we’re exposed throughout our lives, and which influence our microbiota and our health.

Diet is certainly part of the exposome, but the exposome is far from limited to diet.
British epidemiologist Christopher P. Wild, who coined the concept, defines the exposome as a complex and dynamic representation of the exposures to which a person is subject throughout their life, incorporating the chemical, microbiological, physical, recreational, and pharmaceutical environments, as well as lifestyle, diet, and infections.

Spend as much time as possible in nature, let children play among plants and animals, avoid self-medication—especially antibiotics—and eliminate sources of microplastics: these are just some of the healthy habits that, together with a nutritious diet, will improve gut health and, by extension, general well-being. 

In practice, what do people actually do for their microbiota? 

However, from theory to practice, the gap remains wide. According to the 2025 Biocodex Microbiota Observatory, awareness may have improved, but “good” behaviors are struggling to keep pace: awareness of microbiota-linked health issues continues to grow, but the number of people taking action remained flat over the last year.
Specifically: 

• a large majority (83%) report eating a balanced and varied diet to ward off a microbiota imbalance; 
• around 3 in 4 respondents said they took part in physical activity (78%) and avoided smoking (77%) to limit the risk of a microbiota imbalance; 
• around half of those surveyed reported consuming probiotics, and around 40% prebiotics, for the benefit of their microbiota; 
• only a quarter of people received key information about the microbiota after being prescribed antibiotics, despite the impact of antibiotics on our gut flora. 

How can awareness be raised among the public about the importance of a balanced microbiota for health?
Recognized as trusted authorities, healthcare professionals may hold the key to encouraging behavioral change.
Stay tuned for updates in our future editions of our Observatory! 

Discover all our content on food and microbiota:

What is a prebiotic?

The first “official” definition of prebiotics was suggested back in 1995. Since then, it has evolved based on breakthroughs in our understanding of the role and inner workings of the human microbiota.^1,2

A potted history

Prebiotics were defined for the first time in 1995 by two scientists, Glenn Gibson and Marcel Roberfoid.³ They described them as “a nondigestible food ingredient that beneficially affects the host by selectively stimulating the growth and/or activity of one or a limited number of bacteria in the colon, and thus improves host health”. This definition underwent various iterations until 2016, when an international panel of experts came to a consensus on “a substrate selectively used by host microorganisms that confers health benefits”.⁴ In layman's terms, prebiotics are substances that target specific microorganisms in our microbiota, the beneficial ones, and “feed” them. In doing so, they improve our health. This means that these substrates (foods) are out-of-bounds to the majority of microorganisms in our microbiota,⁵ especially to bacteria that can make us ill, such as certain species of clostridia and E. coli!⁶

Some things change, some things stay the same: prebiotics today and tomorrow

According to the 1995 definition, only certain compounds from the carbohydrate family would be classed as prebiotics.⁷ The word “substrate”, which has recently been preferred by experts, extends the concept of prebiotics beyond carbohydrates to anything that specifically feeds bacteria in the microbiota and thus improves our health.^8,9 In addition, prebiotics can work in other areas of the body with a microbiota, not just the intestines. They can support the skin, mouth, and vagina.¹⁰ 
Neither the first nor the most recent definition specifies which microorganisms are targeted by prebiotics. Historically, these have been bifidobacteria and lactobacilli, known to be beneficial for our health and also used as probiotics.¹¹ They are still the most commonly tested and used as a target for prebiotics. However, we now know that other microorganisms can metabolize prebiotics and contribute to our good health.¹² Researchers are turning their attention to prebiotics able to stimulate species such as Propionibacterium, Faecalibacterium, Eubacterium, Akkermansia, and Roseburia.^13,14

Requirements for a “prebiotic”

The definition may have been extended,¹⁵ but this doesn’t mean any old product can call itself a prebiotic!

Before a product can be classified as prebiotic, its chemical structure must first be clearly described. Preclinical laboratory studies must then be conducted, followed by clinical trials in humans, to confirm:

• Its resistance to digestive enzymes (e.g., stomach acid and bile) allowing it to reach the target microbiota (e.g., gut microbiota) intact;
• its selectivity and action on the target microorganisms;
• how it affects the microbiota and its measurable health benefits;
• the effective dose with no side effects.^16,17,18

Sources, functions, mechanism of action... Prebiotics

Find out what prebiotics look like, where to find them, and how they target our beneficial microbes.

Time for some chemistry: what are prebiotics? 

Nowadays, most compounds classified as prebiotics belong to the family of complex carbohydrates: oligosaccharides and polysaccharides.^25,26 Oligosaccharides are chains, or polymers, of several simple sugars or monosaccharides (usually between 3 and 10), such as glucose, fructose, and galactose. Polysaccharides contain more than 20;²⁷ However, some of the rarer prebiotics contain only two sugars; these are known as disaccharides.

The main prebiotics are

FOS (including inulin) and GOS are the prebiotics whose effects on the beneficial microbes in our intestinal microbiota and on our health are most scientifically recognized. They are therefore currently the “stars” of the prebiotic world;^32,33 The recommended dose for a prebiotic effect in adults is 5-8 g FOS or GOS per day.³⁴

However, other substances are being tested for their prebiotic potential, such as:

• Other complex carbohydrates (fibers): xylo-oligosaccharides (XOS), isomalto-oligosaccharides (IMO), polydextrose, soybean oligosaccharides (SBOS), beta-glucans, and pectin;
• Starch derivatives, such as polyols: sorbitol, maltitol, etc.;
• Polyunsaturated fatty acids; o Polyphenols: such as cocoa and tea.^35,36,37,38

Where exactly can you find them?

Prebiotics are found naturally in many fruits and vegetables and in breastmilk. They are also added to foods, such as cookies, cereals, drinks, and dairy products, as well as to baby food.⁴¹ Finally, they are available as dietary supplements,⁴² alone or combined with probiotics, vitamins, minerals, or plant extracts, etc.

Natural sources of prebiotics

Many fruits, vegetables, cereals, and other natural foodstuffs contain prebiotics. For example: 

• Artichokes, chicory root, leeks, asparagus (which contain inulin);
• Bananas, garlic, onions, honey, wheat (which contain FOS);
• Soy and oat milk, cashew nuts, lupins, chickpeas, and pistachios (which contain GOS).^43,44

These foods contain small quantities of prebiotics and eating them only occasionally will not have any significant effect on your health.⁴⁵

Our hunter-gatherer ancestors ate lots of foods containing natural prebiotics, consuming up to about 135 g per day. However, this is quite uncommon with our modern Western diets, which usually only provide us with 1-4 g a day in the US, and 3-11 g a day in Europe.⁴⁶

Prebiotics are now manufactured industrially, either isolated from foods rich in prebiotic substances or made synthetically from sugars, such as fructose, lactose, or sucrose.^47,48,49

What are prebiotics for?

Imagine your microbiota like a garden, where prebiotics are the “fertilizer” that help beautiful plants grow taller, but not the pesky weeds! So, the whole body benefits.

Just like fertilizer, prebiotics aren't “essential” for feeding the microbes in our microbiota. But they do stimulate the growth and activity of microorganisms that are beneficial for our health. This means they help rebalance our microbiota, especially by increasing the ratio of beneficial bacteria to pathogenic bacteria, allowing the microbiota to correctly perform its role of digestion, absorption of nutrients, supporting our natural defenses, etc.^50,51

During fermentation, prebiotics also help bacteria to produce other substances that help the body and our health.⁵² For example, they increase the production of lactate and the short-chain fatty acids (SCFAs) acetate, propionate, and butyrate, which act in the intestine and travel around the rest of the body in the bloodstream.⁵³ They are a source of energy for the body and play important roles for our health, such as maintaining the integrity of the intestinal barrier, and regulating the metabolism of sugars and fats.⁵⁴

Finally, these SCFAs lower the pH in our colon (making it more acidic), which also has health benefits, such as better absorption of nutrients, and more effective protection against microbes.^55,56

How can prebiotics improve our health?

Prebiotics are a relatively new field of science, and there are fewer clinical studies on their health effects than for probiotics.⁵⁹ However, results suggest that by supporting the growth and metabolism of beneficial bacteria in the microbiota,⁶⁰ prebiotics contribute to several main essential bodily functions, making it better equipped to combat various situations.⁶¹

Dynamic research for uncovering new benefits

Studies are currently under way into other potential health benefits of prebiotics, mainly involving animal models, with promising initial results. For example, prebiotics may help combat the malignant transformation of cells. In fact, their fermentation products, such as butyrate, could provide protection from colorectal cancer. Some prebiotics could also help improve memory and concentration in the elderly, or even slow down cognitive decline in diseases such as Alzheimer’s. Finally, they could lower triglyceride levels in the blood, which would help improve the health of the cardiovascular system. Although there is mounting evidence as to the benefits of prebiotics, much more scientific work is needed before learned societies can release further recommendations as to their use.^85,86

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