The vaginal microbiota is still poorly understood, although knowledge is slightly better this year

• Once again this year, only one in five women claim to know exactly what the “vaginal microbiota” is (22%, +2 points vs. 2023, vs. 20% men and women combined). Awareness of the term is greater compared to last year, but remains low: nearly half of women have still never heard of it (48%, -5 points vs. 2023, vs. 51% of men and women combined).
   
• Women are more familiar with the term “vaginal flora”, even if knowledge of the term remains superficial: only one woman in two knows exactly what it is (53% vs. 42% for men and women combined).
   
• A degree of good knowledge about certain characteristics of the vaginal microbiota: almost 7 out of 10 women know that antibiotics can alter the vaginal microbiota (69%) and that vaginal dryness/dehydration has consequences for the vaginal microbiota (69%).
   
• Knowledge is still too weak, but improving on last year: 55% of women know that from childhood to menopause, a woman’s vaginal microbiota does not remain the same (+6 points vs. 2023), and 44% know that bacterial vaginosis is associated with an imbalance in the vaginal microbiota (+8 points vs. 2023).
   
• However, knowledge about many aspects of the vaginal microbiota remains very limited: only 1 in 2 women knows that smoking has an impact on the vaginal microbiota (55%) and 3 in 10 women know that the vaginal microbiota is balanced when its bacterial diversity is low (30%; +2 points vs. 2023)
   

This year, more and more women are adopting behaviors aimed at protecting the vaginal microbiota, even if certain bad practices persist

• The adoption of behaviors to protect the vaginal microbiota varies: while women are very likely to wear cotton underwear (86%, +2 points vs. 2023), other beneficial behaviors are less common. Around 2 out of 3 women avoid self-medication (63%), and 3 out of 5 use a soap-free cleansing solution (61%, +3 points vs. 2023).
   
• Certain behaviors that are harmful to the vaginal microbiota remain ingrained: despite a reduction compared to last year, more than 2 out of 5 women still practice vaginal douching (42%, -3 points vs. 2023), and 53% sleep in their underwear (+1 point vs. 2023).
   

More education from healthcare professionals, which must be stepped up to meet women's needs

• Healthcare professionals delivered more education about the vaginal microbiota this year: 43% of women have received an explanation about the vaginal microbiota (+7 points vs. 2023). Nearly half of women have been made aware of the importance of protecting their vaginal microbiota as much as possible (+8 points vs. 2023). A similar proportion of women stated that a healthcare professional has explained the behaviors to adopt to protect their vaginal microbiota as much as possible (48%, +7 points vs. 2023). Although this progress is noteworthy, it only concerns a minority of women, illustrating room for improvement in the information passed on by healthcare professionals concerning the vaginal microbiota.
   
• This is especially true since women have been widely requesting this kind of awareness-raising. 88% would like to be better informed about the importance of the vaginal microbiota and its impact on health (+2 points vs. 2023).

Age is a determining factor when it comes to the vaginal microbiota: people aged 60 and over are less aware, in contrast to 25-34 year-olds and young mothers

Once again this year, women aged 60 and over remain the least informed and aware of the vaginal microbiota, even though they are more exposed to health problems.
 

• Only 41% of women aged 60 and over know what the vaginal microbiota is, compared with 52% of women overall.
   
• They also lack knowledge of the role and functions of the vaginal microbiota: less than half of women aged 60 and over (49%) know that the vagina is self-cleaning (vs. 56% of all women), and only 39% know that bacterial vaginosis is associated with an imbalance in the vaginal microbiota (vs. 44% of all women).
   
• Despite these knowledge gaps, women aged 60 and over stand out for adopting certain behaviors aimed at preserving the balance of the vaginal microbiota. Thus, 3 out of 4 of them avoid relying on self-medication (76%, vs. 63% of all women) and 67% avoid practicing vaginal douching (vs. 58% of all women). However, fewer of the women aged 60 and over use a soap-free cleansing solution (56%, vs. 61% of all women) and sleep without underwear (43%, vs. 47% of all women).
   
• This population has received less education from healthcare professionals: only a third of women aged 60 and over have received an explanation about the vaginal microbiota from a healthcare professional (32%, vs. 43% of all women).
   

Women aged 25 to 34 and mothers of children under 3 appear to be more informed and aware of the vaginal microbiota.

• 62% of 25-34 year-olds and 60% of mothers of children under 3 know what the vaginal microbiota is (vs. 52% of all women).
   
• A better understanding of the vaginal microbiota: 69% of 25-34 year-olds and 67% of mothers know that every woman has a unique vaginal microbiota (vs. 64% of all women). More of these women also know that the vagina is self-cleaning: 61% of 25- 34 year-olds and 60% of mothers know this (vs. 56% of all women).
   
• More of these women have adopted certain behaviors that are beneficial for their vaginal microbiota: 2 out of 3 use a soap-free cleansing solution (67% of 25-34 yearolds and 71% of mothers of children under 3, vs. 61% of all women), and 54% sleep without underwear (vs. 47% of all women).
   
• 54% of 25-34 year-olds and 55% of mothers of children under 3 have received information from a healthcare professional about the vaginal microbiota (vs. 43% of all women).
   

The International Microbiota Observatory also revealed striking contrasts between countries in terms of knowledge, behaviors and information provided by healthcare professionals. The complete results are available on the Biocodex Microbiota Institute website.

About the Biocodex Microbiota Institute

The Biocodex Microbiota Institute is an international knowledge hub dedicated to human microbiotas. Available in 7 languages, the Institute is aimed at both healthcare professionals and the general public, to raise awareness of the vital role that this part of the body plays in our health. The primary mission of the Biocodex Microbiota Institute is educational: to promote the importance of the microbiota for everyone.

^BMI-24.21

The gut microbiota could one day be a therapeutic target of choice in the fight against cardiovascular disease. So suggests a study conducted by American researchers at Massachusetts General Hospital. ¹

They have just demonstrated that there are numerous associations between gut bacteria and metabolic parameters of cardiovascular health. The strongest links concern certain bacteria capable of metabolizing cholesterol. 

In-depth data on the relationship between the microbiota and the host metabolism

To reach this conclusion, the researchers drew up a complete profile of the gut environment of over 1,400 individuals in the Framingham Health Study. They carried out metagenomic sequencing (analysis of the genomes of all gut microorganisms) and metabolomic sequencing (analysis of all metabolites) of the stools of all the volunteers.

They then investigated whether there were any correlations between the microbiota data and the volunteers' health parameters (triglycerides, cholesterol, C-reactive protein, blood sugar, glycated hemoglobin, blood pressure, etc.).

Bacteria equipped to break down cholesterol

By cultivating three in vitro isolates, the team demonstrated that Oscillibacter were able to absorb cholesterol and transform it into cholestenone, cholesteryl glucoside and hydroxycholesterol, metabolites that could be broken down by other bacteria and ultimately excreted by the body. 

Furthermore, it appeared that the simultaneous presence in the volunteers' microbiota of Oscillibacter and Eubacterium coprostanoligenes (bacteria carrying a gene called ismA involved in cholesterol metabolism) was associated with a more marked reduction in blood cholesterol levels. According to the researchers, the two types of bacteria could have a positive synergistic effect on cholesterol levels.

A vast field of research ahead

The advantage of this study compared with previous studies is that it provides a more complete and detailed understanding of the metabolic pathways by which bacteria act on the body. 

It also lays the foundations for future studies targeting how changes in the microbiota contribute to cardiovascular disease, including how different bacterial communities interact with each other to affect health. 

Murine models have demonstrated that the breasts harbor a microbiota capable of modulating carcinogenesis and the efficacy of chemotherapy. Hence the work published in 2024 by a Chinese team ¹ investigating the involvement in breast cancer of the bacterium Bacteroides fragilis, and more specifically its enterotoxigenic strain (ETBF), which produces the proteolytic toxin BFT-1, known to induce diarrhea and colonic lesions when present in the digestive system.

Tumor microbiota predicts resistance to treatment

First finding: in breast cancer, the presence of ETBF bacteria in tumors is associated with a poor response to neoadjuvant (sidenote: Neoadjuvant therapy Treatment administered prior to surgery or radiotherapy. It generally aims to reduce the size of the cancer, enabling less extensive surgery and/or a smaller radiotherapy field.   Explore MSD Manual ) taxane-based chemotherapy, one of the main therapeutic strategies for breast cancer, particularly triple-negative breast cancer. Further experiments, this time in mice, indicate that the presence of the toxin BFT-1 and activation of the NOD1 receptor in mammary tumors predict a poor response to chemotherapy. The BFT-1 toxin and the NOD1 receptor are thus thought to be involved in chemoresistance in breast cancer, which could justify profiling the tumor microbiota in breast cancer: these biomarkers could predict potential failure and enable treatment to be fine-tuned in advance, thereby improving the response to chemotherapy.

A new chain of mechanisms deciphered

Further in vitro research and research using mouse models also enabled the team to understand the underlying mechanisms. This research showed how the ETBF tumor bacterium is capable of mediating chemoresistance in breast cancer: the toxin BFT-1, secreted by ETBF, binds to the NOD1 receptor; NOD1 interacts with the protein kinase GAK, which phosphorylates the NUMB tumor suppressor to enhance its lysosomal degradation; the NOTCH1-HEY1 signaling pathway is inactivated, inducing multiplication of breast cancer stem cells.

Conversely, inhibition of NOD1 and suppression of the ETBF bacterium significantly increase the efficacy of chemotherapy by suppressing breast cancer stem cells.

Many more questions remain

However, contradictory roles for NOD1 in tumor progression have been reported: NOD1 can, as in this study, promote tumor progression (ovarian, esophageal, and colon cancers) or conversely induce cell apoptosis and inhibit cell proliferation (papillary thyroid carcinoma, hepatocellular carcinoma).

Another point to elucidate: the microbiota of the mammary glands and their tumors are complex, so much so that the dysbiosis associated with cancer is unlikely to be limited to a single species. Thus, other tumor taxa such as Clostridia, Alphaproteobacteria and Actinobacteria are also enriched in patients who do not respond to treatment. Further studies are therefore required to determine all the bacteria involved.

Having microbiota is not only the prerogative of the digestive tract or the skin. Our lungs, our bones, but also our breasts, have their own microbiota too, albeit much smaller than that of the digestive tract, but present nonetheless. And this has serious implications: these organ microbiota are capable of modulating the development of cancer, as well as the efficacy of chemotherapy treatments.

That is why one team has been investigating the involvement of the bacterium Bacteroides fragilis in breast cancer. More specifically, the team focused on a specific strain of B. fragilis, capable of producing a toxin that induces diarrhea and colonic lesions when the bacterium settles in the digestive tract.

A gut bacterium that reduces the effectiveness of chemotherapy

Why this bacterium? Because, in the case of breast cancer, the more this bacterium is present in the tumor, the poorer the response of women to certain chemotherapies (taxane-based treatment, used in particular for triple-negative cancers (sidenote: Triple-negative breast cancer This type of cancer is highly aggressive because it spreads rapidly to other organs. It affects women under 40 of African or Asian origin, in particular. Sources:
(1) https://www.who.int/news-room/fact-sheets/detail/breast-cancer 
(2) https://cancer.ca/en/cancer-information/cancer-types/breast/what-is-breast-cancer/cancerous-tumours/triple-negative-breast-cancer ) ).

To better understand the mechanisms involved, the researchers carried out experiments in mice and demonstrated the cascade of reactions triggered by the bacterial toxin, which ends up promoting the multiplication of cancer cells. Among the players in this cascade is a receptor called NOD1, which is much more present in the tumors of women whose tumors do not respond to chemotherapy.

Should we profile breast microbiota to refine treatment?

Many questions remain, of course. For example, is this tumor bacterium the only one to interact with cancer cells and chemotherapy, given that several other bacteria (Clostridia, Alphaproteobacteria and Actinobacteria) are more numerous in tumors? Why does the NOD1 receptor promote certain cancers (ovarian, esophageal and colon cancers) but seem to slow down others (papillary thyroid carcinoma, hepatocellular carcinoma)?

A recent study led by Prof. Arnout Bruggeman and his team at Ghent University Hospital reveals promising results for using faecal microbiota transplantation (FMT) to treat motor symptoms in Parkinson’s disease (PD). This innovative approach highlights the potential of gut microbiome modulation as a therapeutic strategy for this debilitating neurological disorder.

A new approach to Parkinson’s

The GUT-PARFECT trial, a double-blind, placebo-controlled phase 2 study, evaluated the safety and efficacy of a single FMT in patients with mild to moderate Parkinson’s disease. Participants, aged 50-65 years, were randomly assigned to receive FMT with either healthy donor stool or their own stool (placebo). The primary goal was to assess changes in the Movement Disorders Society-Unified Parkinson’s Disease Rating Scale (MDS-UPDRS) motor score over 12 months.

Surprising findings

One of the most surprising findings was the sustained response in the placebo group. Up to six months post-FMT, patients who received their own stool also showed notable improvements, although less pronounced than those in the healthy donor FMT group. This suggests that even autologous FMT can influence the gut microbiome in ways that may impact motor symptoms, emphasizing the complex role of the gut-brain axis in Parkinson’s disease.

The study also found significant improvements in colon transit time in the healthy donor FMT group compared to the placebo group.  Better gastrointestinal function is particularly relevant for PD patients, who often suffer from severe constipation. However, from the patients’ perspective this difference, was too minimal to result in a noticeable clinical improvement, and the patient-reported scores on the Wexner Constipation Scale have remained no significant between the groups.

Safety first and treatment next

Safety was a crucial aspect of this study. The FMT procedure was well-tolerated, with only mild and transient gastrointestinal symptoms reported, such as abdominal discomfort, which resolved within a week. No severe adverse events were observed, supporting the safety profile of FMT.

The GUT-PARFECT trial's results open up exciting possibilities for Parkinson’s disease treatment. If larger studies corroborate these findings, FMT could become a valuable tool in the therapeutic arsenal against PD. The future of Parkinson’s treatment may well lie in our gut. By harnessing the power of the microbiome, patient could pave the way for more effective and comprehensive management strategies for this challenging condition.

While the strong usually eat the weak, every year the minuscule mosquito causes hundreds of millions of cases of severe or even fatal disease by transmitting parasites (malaria) or a wide variety of viruses to humans through their bites, e.g. flaviviruses (sidenote: Flavivirus is a genus of viruses which consists of >70 members including several that are considered significant human pathogens. Transmitted to humans through the bite of infected mosquitoes, Flaviviruses display a broad spectrum of diseases that can be roughly categorised into two phenotypes:
- systemic disease involving haemorrhage (Dengue and yellow Fever virus)
- and neurological complications (West Nile and Zika viruses) Explore https://pubmed.ncbi.nlm.nih.gov/34696709/ ) (Dengue (sidenote: Dengue viral infection transmitted to humans through the bite of infected mosquitoes. Most people with dengue have mild or no symptoms and will get better in 1–2 weeks. Rarely, dengue can be severe and lead to death. If symptoms occur, they usually begin 4–10 days after infection and last for 2–7 days: high fever (40°C/104°F), severe headache, pain behind the eyes, muscle and joint pains, nausea, vomiting, swollen glands, rash. Individuals who are infected for the second time are at greater risk of severe dengue. There is no specific treatment for dengue. Explore https://www.who.int/en/news-room/fact-sheets/detail/dengue-and-severe-dengue ) , Zika (sidenote: Zika viral infection transmitted primarily by Aedes mosquitoes, which bite mostly during the day. Most people with Zika virus infection do not develop symptoms; those who do typically have symptoms including rash, fever, conjunctivitis, muscle and joint pain, malaise and headache that last for 2–7 days. Zika virus infection during pregnancy can cause infants to be born with microcephaly and other congenital malformations as well as preterm birth and miscarriage. There is no specific treatment available for Zika virus infection or disease. Explore https://www.who.int/news-room/fact-sheets/detail/zika-virus ) , etc.), alphaviruses (sidenote: Alphavirus genre de virus comprenant 27 virus dont le redouté (et imprononçable) Chikungunya, qui après un délai d’incubation de 2 à 10 jours, provoque une fièvre et des atteintes articulaires sévères. Les alphavirus sont transmis par la piqûre d’un moustique infecté. Explore https://www.ncbi.nlm.nih.gov/books/NBK7633/ ) (Chikungunya), etc. What if the solution is not to eliminate the mosquito (insecticides) or keep it at bay (mosquito nets, repellent), but simply to prevent it from catching the virus and transmitting it to humans? 

Protecting the mosquito...

This serious solution has been put forward by a Chinese team based on their work on the gut microbiota of mosquitoes. Among the 55 bacteria present in the insects’ digestive tract, one – Rosenbergiella YN46 – caught their attention. Why? Because it permanently prevented the mosquitoes that ingested it from catching flaviviruses.

How is this possible? This bacterium takes up permanent residence in the mosquito’s digestive tract, where it transforms glucose (sugar) into an acid. As a direct consequence, the digestive tract contents become highly acidic, spoiling the flaviviruses. Unable to infect mosquitoes, these viruses will not then infect humans.

...to protect humans

The researchers did not confine themselves to laboratory work. They confirmed their idea in the field. They observed that, in the prefectures of the Chinese province of Yunnan in which Dengue wreaks havoc, mosquitoes rarely harbor the bacterium in their digestive systems. Conversely, in prefectures where only a few isolated cases of dengue fever have been reported, the majority or almost all mosquitoes (91.7% in Wenshan prefecture) carry the bacterium.

The good news is that not only is it easy to inoculate mosquitoes with the bacterium (you just need a bowl of sugar water containing the bacterium), but that the insect retains it throughout its life (from aquatic larvae to winged adult) and passes it on to the next generation. In other words, inoculation with the protective Rosenbergiella YN46 bacterium lasts for life and is passed on to the mosquito’s offspring.

Infections caused by Gram-negative bacteria (sidenote: Gram-negative bacteria A group of bacteria characterized by their unique cell wall structure, which makes them resistant to many antibiotics and often more challenging to treat. ) are becoming more common and are often treated with broad-spectrum antibiotics, which can disrupt the gut microbiome and lead to secondary infections. There is a pressing need for antibiotics that are selective for pathogenic Gram-negative bacteria while sparing commensal bacteria and the gut microbiome.

This new study ¹ aimed to design and discover a Gram-negative-selective antibiotic that targets the Lol lipoprotein transport system, thereby preserving the gut microbiome and preventing secondary infections.

Crafting a selective antibiotic

The development process began with a series of whole-cell screens at AstraZeneca, identifying compounds that inhibit the LolCDE complex, a critical component of the Lol system. Researchers prioritized compounds that showed initial promise but faced challenges in solubility and resistance. Through an iterative chemical modification process, they engineered a hybrid scaffold, appending primary amines to enhance compound accumulation and targeting efficiency.

The culmination of these efforts was the identification of lolamicin (sidenote: Lolamicin A newly developed Gram-negative-selective antibiotic that targets the Lol lipoprotein transport system, effectively killing pathogenic bacteria without disrupting the gut microbiome. ) , a compound that effectively disrupts the Lol system, thereby selectively killing pathogenic Gram-negative bacteria. This selective targeting is made possible by the significant sequence homology divergence between pathogenic bacteria and commensal gut bacteria, ensuring that beneficial bacteria remain unharmed.

Achieving breakthrough results in infection models

The efficacy of lolamicin was put to the test in rigorous preclinical studies, and the results were nothing short of groundbreaking. Lolamicin demonstrated potent activity against a diverse panel of over 130 multidrug-resistant (sidenote: Multidrug-resistant Describes bacteria that have developed resistance to multiple classes of antibiotics, making infections caused by these bacteria particularly difficult to treat. ) clinical isolates of Gram-negative bacteria, including notorious pathogens such as E. coli, Klebsiella pneumoniae, and Enterobacter cloacae.

One of the standout features of lolamicin is its microbiome-sparing capability. Unlike broad-spectrum antibiotics that wreak havoc on the gut microbiome, lolamicin treatment resulted in minimal changes to the gut microbial composition. This was evidenced by full-length 16S rRNA sequencing of fecal samples from treated mice, which showed that lolamicin preserved the diversity and richness of the gut microbiome. Remarkably, mice treated with lolamicin retained their ability to spontaneously clear Clostridioides difficile colonization, a common and severe complication associated with antibiotic use.

As Gram-negative (sidenote: Gram-negative bacteria A group of bacteria characterized by their unique cell wall structure, which makes them resistant to many antibiotics and often more challenging to treat. ) bacterial infections rise, our gut microbiome—home to trillions of beneficial bacteria—is under siege from broad-spectrum antibiotics. These drugs, though effective against infections, often wipe out our gut’s beneficial bacteria, leading to secondary infections. It's like using a sledgehammer to crack a nut. There’s an urgent need for antibiotics that zero in on the bad guys without harming the good ones.

This is where lolamicin comes in. Researchers have been working to design an antibiotic that specifically targets Gram-negative bacteria ¹.

The secret weapon? The Lol lipoprotein transport system, a critical mechanism exclusive to these harmful bacteria. By disrupting this system, lolamicin can take out the pathogens while leaving our beneficial bacteria unscathed.
 

Precision medicine: the art of crafting lolamicin

Developing lolamicin (sidenote: Lolamicin A newly developed Gram-negative-selective antibiotic that targets the Lol lipoprotein transport system, effectively killing pathogenic bacteria without disrupting the gut microbiome. ) was no small feat. Imagine trying to craft a key that perfectly fits a lock without disturbing the surrounding structure. Researchers began with whole-cell screens, identifying compounds that could inhibit the Lol system in a group of specific bacteria. Through a series of tweaks and modifications, they engineered a hybrid scaffold that led to the creation of lolamicin.
 

This new antibiotic was put through rigorous tests and delivered impressive results. Lolamicin showed potent activity against over 130 different strains of multidrug-resistant bacteria (sidenote: Multidrug-resistant Describes bacteria that have developed resistance to multiple classes of antibiotics, making infections caused by these bacteria particularly difficult to treat. ) , including notorious troublemakers like E. coli and Klebsiella pneumoniae. In mouse models of severe infections, lolamicin significantly reduced bacterial loads and improved survival rates, outperforming existing antibiotics.

Targeting the villains, sparing the heroes

But the real game-changer is lolamicin’s ability to preserve the gut microbiome. Unlike broad-spectrum antibiotics that ravage the gut's bacterial community, lolamicin treatment resulted in minimal changes. This was confirmed through advanced DNA sequencing techniques, which showed that the diversity and richness of the gut microbiome were maintained. Remarkably, lolamicin-treated mice could fend off secondary infections from Clostridioides difficile, a common complication of antibiotic use.
 

Although further validation in human trials is needed, lolamicin represents a revolutionary step forward. It's not just about fighting infections—it's about doing so with precision, ensuring our beneficial bacteria remain unharmed. This advancement heralds a new era in medicine, where antibiotics are tailored to target pathogens precisely, safeguarding our overall health.

Little known to the general public, functional dyspepsia (FD) is a very common gastrointestinal disorder that is under-diagnosed and still poorly understood today. FD accounts for 3% to 5% of GP visits in North America ¹ !

Functional dyspepsia’s varied symptoms are always associated with a feeling of poor digestion ²:

• feeling full long before you’ve finished your meal 
• the feeling of having eaten too much (stomach feels heavy and bloated), despite having eaten a perfectly reasonable-sized meal
• pain or burning in the upper stomach
• loss of appetite
• belching or hiccups
• nausea or even vomiting

Did you know?

The disorder is called functional dyspepsia since it is not accompanied by any structural abnormality in the digestive organs and tissues. Symptoms cannot be explained by the presence of a lesion in the stomach (no ulcers) or any other organic or structural abnormality: all tests (gastroenteroscopy, ultrasound, CT scan, etc.) come out negative.

How common is the disease? Who is most at risk?

Studies suggest that 10% to 30% of adults and 3% to 27% of children worldwide are affected by functional dyspepsia ². Women, smokers, and users of non-steroidal anti-inflammatory drugs (ibuprofen, ketoprofen) are at greater risk ³.

The consequences for patients are far from negligible: two-thirds of those affected by functional dyspepsia suffer from persistent and irregular symptoms that can affect their quality of life and well-being ¹.

Diet

Increasingly clear is the role played by diet in triggering functional dyspepsia symptoms. The culprits? Above all, fatty foods. But they’re not alone. Carbohydrate-containing foods, milk and dairy products, citrus fruits, spicy foods, coffee, and alcohol, have also been implicated ⁵. However, the results of these studies remain uncertain.

The mind may also play a role, with the memory of a bad experience leading patients to anticipate symptoms and over-experience them when exposed again. Experience has shown that distracting a patient with a cognitive task is enough to make them forget about their symptoms. Conversely, stating that the fat content of a yogurt is higher than it actually is increases the nausea felt by patients

Stress and anxiety

functional dyspepsia patients are often stressed and anxious: one large study showed that anxiety was clearly linked to the disease, and more specifically to postprandial distress; another study of 18,000 Japanese showed that patients with functional dyspepsia symptoms felt more stressed on a daily basis, more often mentioned not getting enough sleep, and complained more of difficulties in falling asleep ⁵.

Lack of physical activity

Functional dyspepsia patients generally report lower levels of physical activity. This is unfortunate since it appears that sport can actually reduce symptoms, and improve transit and gas evacuation in people suffering from bloating ⁵.

Tobacco

A study of 2,560 Swedes shows that smokers are at greater risk of postprandial distress syndrome: smoking 10 to 19 cigarettes a day increases the risk by 42%, while smoking more than a pack a day more than doubles the risk ⁷.

Obesity

Obesity is associated with many gastrointestinal symptoms, including functional dyspepsia. Several hypotheses have been put forward: for example, in obese people, the oral and gut receptors responsible for alerting the body to the presence of fats may be altered, amplifying the gastrointestinal effects in these patients, making them more sensitive to dietary fats ⁵.

Some specialists also point to a reciprocal link between functional dyspepsia and metabolic syndrome (sidenote: Metabolic syndrome Metabolic syndrome, also known as syndrome X, is characterized by the accumulation of several metabolic disorders in the same individual, including a large waist circumference (due to excess abdominal adipose tissue), hypertension, abnormal fasting blood sugar levels or insulin resistance, and dyslipidemia.  ) , with each promoting the other, creating a vicious circle ¹.

Helicobacter pylori bacteria

Since the 1980s, it has been known that the stomach, although highly acidic, is not sterile. It even harbors a community of microorganisms, including the bacterium H. pylori. However, infection by H. pylori appears to lead to the onset and progression of functional dyspepsia: patients with a history of H. pylori infection have a higher risk of developing functional dyspepsia ².

Dysbiosis throughout the digestive system

The digestive tract is home to almost 100 billion microorganisms from over 1,000 different species, which together are known as the gastrointestinal microbiota.

Proteobacteria, Firmicutes, Actinobacteria, and Bacteroidetes dominate this community, making up more than 98% of the gut microbiota, with Firmicutes predominating, followed by Actinobacteria and Bacteroidetes ². At least in healthy patients. In those suffering from illnesses such as functional dyspepsia, this balance is not found; instead, dysbiosis is observed throughout the digestive system, from mouth to anus ².

In functional dyspepsia patients, studies have found, for example:

• a higher abundance of Firmicutes, streptococcus (associated with symptoms in the upper stomach), Bifidobacterium and Clostridium
• a lower abundance of Prevotella (accompanied by more symptoms of discomfort after eating)

The role of microbial metabolites

The microbiota’s role in functional dyspepsia is far from limited to the bacteria present, since each of these bacteria secretes various active molecules, both beneficial and harmful, that are closely linked to host health and to the onset and progression of numerous diseases ^2,3. For example: 

• some bacterial metabolites have a beneficial effect (e.g. short-chain fatty acids (sidenote: Short chain fatty acids (SCFA) Short chain fatty acids (SCFA) are a source of energy (fuel) for an individual’s cells. They interact with the immune system and are involved in communication between the intestine and the brain. Silva YP, Bernardi A, Frozza RL. The Role of Short-Chain Fatty Acids From Gut Microbiota in Gut-Brain Communication. Front Endocrinol (Lausanne). 2020;11:25. )  produced by Firmicutes) 
• while others are harmful to the host (e.g. pro-inflammatory sphingolipids produced by Bacteroidetes and Prevotellacae) ³

While many gray areas remain, researchers believe that the mechanisms behind functional dyspepsia are likely to be multifactorial and vary from patient to patient ⁸. Thus, a range of mechanisms are involved in functional dyspepsia:

Disruption of the gut barrier

In normal circumstances, food passing through our digestive system remains isolated from our body by a barrier, the intestinal mucosa. This barrier is semi-permeable: it allows nutrients to be absorbed but bars passage to the various harmful substances and pathogens ingested along with our meal ². 

In functional dyspepsia patients, the integrity of this mucosa is compromised, so much so that it performs its filtering role less effectively

Disruption of gut immunity

In functional dyspepsia patients, there appears to be an excessive immune response: 40% of patients present inflammatory cells infiltrated into the duodenum, while a proliferation of bacteria (particularly oral bacteria) ⁹ is frequently observed in the small intestine, which may activate this immune response. Indeed, some researchers believe that a greater focus on the microbiota of the small intestine (sidenote: Small intestine Section of the digestive system between the stomach and the large intestine (i.e. the colon) essential for the digestion and absorption of nutrients. Measuring 21 to 23 feet, it is the longest portion of the digestive tract, comprising the duodenum, then the jejunum, and finally the ileum.  ) is required in order to better understand the pathogenesis of functional dyspepsia ⁹.

Deregulation of the gut-brain axis

There are complex interactions between the gut microbiota, the digestive system, and the central nervous system. This microbiota-gut-brain axis explains why stress can cause stomach ache, or why changes in the gut flora can alter intestinal motility and “inform” the brain, which in turn can regulate the gut. However, functional dyspepsia has been shown to be closely linked to gastrointestinal motility disorders (which are under cerebral control) and to gastrointestinal hypersensitivity, all of which are linked to the gastrointestinal microbiota ². From here to suggesting that everything is linked is only a short step...

An abnormal response to food ingestion

The presence of nutrients in the interior of the digestive tract produces signals that alter digestion. For example, a high-fat meal emains in the stomach longer, since gastric emptying is delayed. In functional dyspepsia patients, food ingestion may be associated with exaggerated signals from the gastrointestinal tract. This results in a whole series of symptoms which bear no relation to reality, such as feeling full when a meal has only just begun, hypersensitivity to gastric distension, and so on. ⁵

Diet

Logically, since diet is thought to play a role in functional dyspepsia, adapting it may improve symptoms. However, there is a dearth of studies highlighting the effects of specific diets. Nevertheless, experts believe that a large proportion of patients would benefit from a lower-fat diet and smaller meals eaten more often. In fact, functional dyspepsia patients are already doing so in practice: they have a slightly reduced dietary fat intake and tend to eat smaller meals more frequently ⁵.

Other patients would benefit more from avoiding spicy or acidic foods (tomatoes, citrus fruits, etc.) or foods rich in fiber or FODMAPs, which cause bloating. However, these restrictions should be managed with care so as to avoid an unbalanced diet ².

Proton pump inhibitors

Proton pump inhibitors (PPIs) are drugs used to reduce gastric acid secretion. They are prescribed by doctors to treat gastroesophageal reflux disease (GERD) and peptic ulcers.

In the short term, proton pump inhibitors (PPIs) may improve functional dyspepsia symptoms. However, their long-term use seems to go hand in hand with an increase in Streptococcus and, thus, a harmful dysbiosis ¹³.

Antibiotics to eradicate H. pylori

According to the American College of Gastroenterology and the Canadian Association of Gastroenterology, functional dyspepsia patients under 60 years of age should first be screened for H. pylori. If the test proves positive, antibiotics should be prescribed to eradicate the bacteria.

However, this strategy has its limits: only 1 in 10 patients will experience an improvement in their symptoms, while the remainder will see their symptoms worsen ¹⁴.

Probiotics

Since dysbiosis of the gastrointestinal microbiota is closely linked to the onset and progression of functional dyspepsia, regulating the gastrointestinal microbiota has logically been put forward as a potential treatment ². The role of probiotics may be multifactorial ¹⁵ :

• restoration of commensal flora eliminated by pathogens
• restoration of gut barrier permeability
• reduction of visceral hypersensitivity
• local and systemic anti-inflammatory action
• regulation of intestinal motility

All these benefits are thought to reduce symptoms of functional dyspepsia ¹⁵.

Alternative therapies

Various alternative therapies have been recognized as safe and effective treatments for functional dyspepsia:

• cognitive behavioral therapy, commonly used to treat stress and anxiety, helps the patient identify the thoughts or behaviors that lead to or exacerbate the expression of symptoms
• hypnotherapy, where the patient, in a state of hypnosis, is more receptive to therapeutic suggestions
• The potential of virtual reality is also being explored ¹⁴.

Introduction

We're about to dive into the fascinating world of "biotics." Now, you might be thinking, "What in the world are 'biotics'?" Well, it all goes back to an ancient Greek word, "bíos," which simply means "life." From that root word, we get terms like probiotics, prebiotics, postbiotics, synbiotics. These aren't just fancy scientific names – they're like the different parts that make up a lively neighborhood, each playing a unique role in keeping things running smoothly.

Imagine you're the new resident on the block, and a friendly neighbor offers to show you around, pointing out all the key people and places that make the community tick. That's what we're doing here – getting a local's tour of the "biotics" neighborhood inside your body.

In our city of health, probiotics are like our visiting beneficial friends – live microorganisms that take up residence within us and contribute to our well-being. As defined by the World Health Organization (WHO) and the International Scientific Association for Probiotics and Prebiotics (ISAPP), probiotics are "live microorganisms which, when administered in adequate amounts, confer a health benefit on the host." ¹

In simpler terms, they are beneficial microbes such as bacteria, yeast, … that support our overall well-being. Probiotics contribute to our health in various ways, such as:

• promoting a balanced microbiome ²
• inhibiting the growth of pathogens inside the human body ³
• improvement in barrier and metabolic functions of targeted organs ^{4, 5, 6}
• supporting immune function ⁷
• and modulation of diverse signaling and metabolic pathways ⁸

One widespread misconception is that all fermented foods, such as yogurt, kefir, or kombucha, are inherently probiotic. ⁹ While fermentation can introduce beneficial bacteria, not all fermented products contain live, probiotic strains that meet the criteria set forth by health authorities. ¹⁰ However, some fermented foods are fermented using a microbe proven to be a probiotic, or have been supplemented with probiotics in sufficient quantities to offer health benefits.

It's essential to carefully read labels and rely on reputable sources to ensure you're consuming products with scientifically and clinically validated probiotic cultures. Additionally, some assume that probiotics are a one-size-fits-all solution, but different strains can have varying effects on different individuals and health conditions. ^{1, 11} Consulting with healthcare professionals and following evidence-based guidelines is crucial for optimizing the benefits of probiotics based on your unique needs and circumstances.

If you want to learn more about probiotics, you can read our dedicated section here:

Prebiotics are defined as "a substrate that is selectively utilized by host microorganisms conferring a health benefit." ^{12, 13} Unlike probiotics, prebiotics themselves are not live microbes but rather serve as fuel for the existing beneficial bacteria in our microbiome. It's a common oversimplification to describe prebiotics as "food for probiotics."

While prebiotics do support probiotic growth, their beneficial effects stem from the activity of the resident gut microbiota, which metabolize these compounds, indirectly conferring physiological advantages to the host – us! Moreover, not all dietary fibers are prebiotics, and not all prebiotics are fibers. ¹⁴ This distinction is often overlooked, leading to misconceptions about their definitions and functions.

Imagine prebiotics as favorite restaurants for your helpful bacteria. Foods like bananas, onions, and garlic are rich in substances such as inulin and galacto-oligosaccharides (GOS) that act as prebiotics. When your beneficial bacteria dine on these foods, they can increase the production of molecules, i.e. metabolites, such as short-chain fatty acids (SCFAs) (sidenote: Short chain fatty acids (SCFA) Short chain fatty acids (SCFA) are a source of energy (fuel) for an individual’s cells. They interact with the immune system and are involved in communication between the intestine and the brain. Silva YP, Bernardi A, Frozza RL. The Role of Short-Chain Fatty Acids From Gut Microbiota in Gut-Brain Communication. Front Endocrinol (Lausanne). 2020;11:25. ) acetate, propionate, and butyrate which in turn can improve your health. ¹⁵

Beyond supporting gut health, prebiotics have been linked to re-balancing the microbiota for better defense against pathogens, ¹⁶ weight management, ¹⁷ better mineral absorption, ¹⁸ etc. Their benefits extend beyond just the gut. ¹⁹

We have also prepared a dedicated section about prebiotics and their health benefits here:

After probiotics have completed their visit of the city, they leave behind gifts known as postbiotics. These are like the products and services that businesses in a city provide after taking in raw materials. Postbiotics include beneficial substances like vitamins and short-chain fatty acids (sidenote: Short chain fatty acids (SCFA) Short chain fatty acids (SCFA) are a source of energy (fuel) for an individual’s cells. They interact with the immune system and are involved in communication between the intestine and the brain. Silva YP, Bernardi A, Frozza RL. The Role of Short-Chain Fatty Acids From Gut Microbiota in Gut-Brain Communication. Front Endocrinol (Lausanne). 2020;11:25. ) . They're the rewards your body gets from the probiotics' hard work.

This definition was revised many times, and the Scientific Community have now reached a consensus: “postbiotic is a preparation of inanimate microorganisms and/or their components that confers a health benefit on the host.” This means that postbiotics are not just the “re-purposed” waste of the probiotics (or their end-products), but they are also the “dead” probiotics themselves and fragment components! ²⁰

Such as probiotics, postbiotics have been shown to strengthen the barrier function, reduce inflammation, and exhibit antimicrobial activity against pathogens, thereby promoting overall health. ²¹ Their beneficial properties also extend beyond the gut with benefits for skin and vaginal health and potentially addressing skin and vaginal conditions. ^{22, 23}

You may have heard additional names such as Parabiotics, Paraprobiotic or Proteobiotics. Indeed, some researchers have tried to define further the different elements or body parts of the postbiotic component, meaning dead cells, components of the cells and the metabolites produced by those microbial cells.

• While Parabiotics and Paraprobiotic are synonymous, they’re used to describe the inactivated microbial cells, either intact or broken; think of them as the "ghosts" of those helpful microbes still being able to lend a hand. ²⁴
• On the other hand, Proteobiotics are natural metabolites produced by the probiotic during fermentation. ^{25, 26}

However, there is no consensus agreement on these possible definitions, and they all fall under the ISAPP definition of Postbiotic. ²⁰

Synbiotics are like community projects that bring everyone together for a common goal. ²⁷ They combine probiotics and prebiotics in a single product, ensuring that the good bacteria not only have a place to live but also plenty of their favorite food right from the start. This combination can be found in some yogurts and dietary supplements, designed to work together to provide an even greater health benefit.

On the other hand, Psychobiotics are a whole new category of probiotics and prebiotics that can actually benefit your mental health when consumed properly. ²⁸ They work through something called the gut-brain axis. Basically, your gut and brain are physically connected and are in constant communication. The microbes living in your intestines can send signals to your brain that impact your mood, cognition, and even behaviors.

Researchers are really excited about the potential of psychobiotics. Early studies show they may help prevent or improve conditions like neurodegenerative diseases like Alzheimer's or Parkinson's. Some evidence even suggests psychobiotics could play a therapeutic role in treating psychiatric disorders like depression or anxiety. ²⁹

You can find out more about the interaction between the gut and the brain here:

What about antibiotics?

Finally, it's essential to differentiate antibiotics from the other "biotics." While antibiotics are crucial life-saving medications for treating bacterial infections, their indiscriminate or excessive use can severely disrupt the delicate balance of the microbiome, potentially causing unintended and far-reaching consequences. ^{30, 31} These powerful drugs don't discriminate between harmful and beneficial bacteria, which means they can decimate the vital microbial populations that promote health and immunity.

Maintaining a healthy, diverse microbiome through probiotics, prebiotics, and other "biotics" can help counteract some of the collateral damage caused by antibiotics and support overall well-being.

You can find here a dedicated section about the effects of antibiotics on the microbiota and on your health:

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