Every clinician knows the trade-off. A course of broad-spectrum antibiotics can be life-saving, but it often leaves the gut microbiome a cleared landscape. This state of dysbiosis (sidenote: Dysbiosis An imbalance in the microbial community, characterized by reduced beneficial bacteria and increased harmful species, potentially leading to adverse health outcomes. ) opens the door for colonization by antibiotic-resistant bacteria, chief among them vancomycin-resistant enterococci (VRE). A new study from INRAe details a precise strategy to rebuild the gut's defenses, not with a sledgehammer, but with a scalpel.

A precision toolkit for microbiota restoration

Rather than relying on the undefined mix of a fecal transplant, researchers used mathematical modeling to rationally design a consortium of seven specific commensal bacteria (sidenote: Commensal bacteria Bacteria that cohabit peacefully with their host, particularly in the gut. They can benefit the host by boosting the immune system, aiding digestion, or fighting pathogens. ) . This live biotherapeutic (sidenote: Live Biotherapeutic Product (LBP) Biological product containing living microorganisms, such as bacteria, and intended to prevent or treat disorders and diseases (vaccines do not fall into this category). Rouanet A, Bolca S, Bru A, et al. Live Biotherapeutic Products, A Road Map for Safety Assessment. Front Med (Lausanne). 2020;7:237. ) , named Mix7, includes strains from the Lachnospiraceae, Ruminococcaceae, Lactobacillaceae, and Muribaculaceae families. When given to mice challenged with Enterococcus, Mix7 didn't just compete for space; it actively accelerated microbiota restoration. The data shows a rapid recovery of the Bacteroidota phylum, a key group often depleted by antibiotics, which correlates with reduced VRE levels.

Functional recovery

This ecological restoration had profound functional consequences. The study found that Mix7 was effective even in a more persistent state of dysbiosis, though not in all subjects, with a 30% to 70% response rate across trials. In "responder" mice, VRE clearance was associated with a complete functional reboot of the gut, marked by higher cecal concentrations of short-chain fatty acids like acetate, propionate, and butyrate, alongside a normalization of bile acid and amino acid profiles.

This variability suggests a powerful clinical application: the initial composition of a patient’s microbiota could serve as a predictive biomarker, allowing for the stratification of patients most likely to benefit from this intervention.

The path to the clinic

The path from bench to bedside appears promising. Critically for translation, five of the seven bacterial species in Mix7 are shared between mice and humans, with the other two possessing direct human functional equivalents. This work provides a clear blueprint for developing targeted biotherapeutics that not only clear a specific pathogen but also restore the host's endogenous defenses. Such strategies represent a vital new front in the fight against antibiotic-resistant bacteria, a key goal highlighted each year during World Antimicrobial Awareness Week (WAAW).

It’s a silent pandemic that grows every year and could become, by 2050, the leading cause of death worldwide, ahead of cancer.
Antimicrobial resistance is under the spotlight of the World Health Organization, which has organized the World Antimicrobial Awareness Week every year since 2015. This initiative aims to raise awareness and improve understanding of antimicrobial resistance, while also promoting coordinated actions to combat the emergence and spread of drug-resistant pathogens.

A cornerstone of scientific information and a key player in educating and training healthcare professionals and the general public on the importance of human microbiota, the Biocodex Microbiota Institute is taking part in this campaign for the sixth consecutive year by offering its audiences an educational, engaging, and interactive workshop: the first awareness mural on antibiotic resistance.

15 minutes to grasp the urgency and take action

Primarily intended for healthcare professionals (general practitioners, pharmacists, pediatricians, hospital staff, and healthcare students), the workshop is designed to be simple, visual, and participatory. It takes the form of a game with 60 cards that allow participants to reconstruct different antibiotic use scenarios and assess their consequences on multiple levels:

• microbiota,
• patient,
• healthcare system,
• society.

The workshop then invites participants to take a step back and reflect on the global risks associated with antibiotic resistance (increasing deaths, pressure on research, and the potential return to a “post-antibiotic era”). Finally, it concludes on a positive note, focusing on concrete, multi-stakeholder solutions: prevention, vaccination, research, responsible prescribing, and the One Health approach. And for the first time, this tool is freely available accessible and downloadable by everyone.

A ready-to-use tool accessible to everyone

Developed in partnership with Querceo, the workshop was designed to be easy to implement:

• Short duration (15 minutes) and a format adaptable to groups of around ten participants
• Can be used during medical congresses, hospital meetings, university courses, or public events.
• No prior scientific knowledge is required. 
• Freely accessible and available in 7 languages. 

By making this tool accessible to everyone, the Biocodex Microbiota Institute aims to achieve several goals:

• Equip healthcare professionals to strengthen their role as mediators with patients and the public, 
• Raise collective awareness around a major health and environmental issue,
• Encourage broad mobilization against antibiotic resistance, as everyone has a role to play. 

Antibiotics have revolutionized modern medicine, saving countless lives. However, their repeated or inappropriate use profoundly disrupts the gut microbiota, reducing its diversity and protective capacity. This dual aspect of therapeutic progress and microbial imbalance highlights the need for judicious use.

To mark the WHO's annual World AMR Awareness Week, The Biocodex Microbiota Institute takes stock.

Repeated exposure to antibiotics can profoundly disrupt the balance of the microbiota, leading to dysbiosis with various clinical consequences. These alterations in the microbiota are now recognized as a risk factor in many diseases. Better understanding them means strengthening prevention and personalizing care.

The widespread and sometimes inappropriate use of antibiotics is making them less and less effective in treating infections, with many bacteria now resistant to antibiotics. Surveillance, research, and awareness remain essential to controlling this major health issue.

Microbiotalk: short conferences on antimicrobial resistance

This Microbiotalk conference aims to illuminate the multifaceted challenges of AMR, exploring the intricate connections between gut microbiota, environmental factors, and public health. Featuring international experts and patient advocates, the event delves into topics such as the impact of antibiotics on the intestinal microbiota, the emergence of resistance in early childhood, environmental reservoirs of resistant bacteria, and the critical role of patient and public engagement.

Every initiative counts in the fight against antimicrobial resistance. Visualizing data, sharing knowledge, and strengthening collaboration among healthcare professionals are essential levers. Collective awareness is at the heart of the global prevention strategy.

Discover the first collage illustrating the challenges of antimicrobial resistance.

After antibiotic treatment, the microbiota takes time to regain its balance. Approaches based on understanding the interactions between antibiotics and intestinal flora are paving the way for new support strategies. This knowledge opens up promising prospects for maintaining a healthy microbiota and preventing post-treatment dysbiosis.

How to rebuild my gut microbiota after taking antibiotics?

How to talk about gut health: Pr. Sokol's advices. This educational video series is designed to help healthcare professionals better communicate with their patients about gut microbiota

The effects of antibiotic resistance extend beyond the clinical sphere: they also affect the environment, the microbiota, and global health. This global phenomenon requires an integrated “one health” approach to be effective. Now is the time for understanding, prevention, and collaboration.

Check out our articles to explore the full range of impacts of resistance and the solutions being considered on a global scale:

Will phages (viruses that target bacteria) soon be part of the therapeutic arsenal for fighting colorectal cancer (CRC)? So suggests a fascinating study published in the journal Cell Host & Microbe. ¹

According to the authors, a gut bacterium found in abundance in those who fail to respond to treatment may be responsible for resistance to chemotherapy. Eradicating this bacterium with phages may make it possible to restore the sensitivity of cancer cells to treatment and thus improve patient survival.

A gut bacterium that worsens prognosis

The scientists asked whether B. fragilis was responsible for chemoresistance. To test their hypothesis, they cultured human cancer cells in the presence of B. fragilis and then with two chemotherapy drugs, 5-fluorouracil (5-FU) and oxaliplatin (OXA).

The results indicated that B. fragilis does indeed reduce the sensitivity of cancer cells to chemotherapy, in particular by suppressing chemotherapy-induced apoptosis. These results were confirmed in vivo in the same experiment on mouse models of CRC, with a greater number of tumors present in mice exposed to B. fragilis than in those not exposed, following treatment with 5-FU and OXA.

An RNA analysis of the cells co-cultured with or without B. fragilis and then treated with 5-FU and OXA showed that B. fragilis upregulates the Notch1 metabolic pathway that appears to underlie the chemoresistance of CRC cells.

Fragilis but formidable

The researchers then asked what interactions between the bacteria and cancer cells activated the Notch1 pathway. Using scanning electron microscopy of cells in vitro and in vivo, they observed that B. fragilis did indeed adhere to cancer cells.

According to the authors, on the surface of the bacteria there is a membrane lipoprotein from the SusD/RagB family that is capable of binding specifically to Notch1 receptors on cancer cells. This binding activates the Notch1 signaling pathway and induces the “epithelial-to-mesenchymal transition”, which corresponds to the first stage of cancer cell dissemination (metastases).
 

Phages to the rescue

To cap off the study, the researchers identified a phage called VA7 that is capable of specifically eliminating B. fragilis safely and effectively. They administered the VA7 phage to CRC mice that had become chemoresistant following exposure to B. fragilis and found that it completely reversed the induced chemoresistance.

This study is particularly interesting because it shows that:

• An abundance of B. fragilis in the microbiota of CRC patients could serve as a non-invasive biomarker to predict the effectiveness of chemotherapy. 
• Combining chemotherapy with VA7 phages in patients with an abundance of B. fragilis could improve clinical response without side effects.
   

To be continued...

Concerned about your health but find it difficult to eat healthily? Need to lose weight but suffer from cravings? Try replacing cereal bars, cookies, and other fatty, sugary, and salty snacks with almonds. A study conducted by researchers at Florida State University ¹ in the United States suggests your gut microbiota would benefit greatly, and so would your health.

Counterbalancing the effects of junk food

People who eat a Western diet often suffer from dysbiosis, while being overweight generally leads to gut imbalances. To find out whether almonds could help remedy this, the scientists recruited 15 overweight or obese adults and divided them into two groups:

• The first group followed a “typical” American diet (high in fat, carbohydrates, meat, processed foods, etc.) 
• The second followed the same diet, but supplemented with 42.5 g of almonds per day (two small handfuls, or about 30 almonds).

After four weeks, all participants returned to a normal diet for 15 days, then switched diets for another four weeks. 
The researchers took stool and blood samples to analyze changes in gut microbiota composition and bacterial metabolites, as well as various health markers.

A microbiome more beneficial to health

The results showed that snacking on almonds enriches the gut microbiota with beneficial bacteria and suppresses pathogenic microorganisms.

Furthermore, these changes are correlated with clear improvements in certain health markers.
By supporting the proliferation of Faecalibacterium prausnitzii, a well-known beneficial bacterium that produces butyrate (a short-chain fatty acid, SCFA (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. ) ), almonds could strengthen the intestinal barrier, reduce inflammation, and promote cardiovascular health. 

By reducing the abundance of pathogenic bacteria such as Ruminococcus torques, these nuts could lead to a health-beneficial reorganization of the microbiota’s ecological niche.

Likely to affect weight and satiety

Almond consumption may also lead to a decrease in certain toxic bile compounds associated with intestinal diseases, particularly colon cancer, and an increase in ketone body levels.

Ketone bodies are molecules produced by the digestion of body fat. The increase in these bodies during the experiment may be linked to the satiating effect of almonds, which encourages the body to use its fat reserves as a source of energy more often.

Lastly, almond consumption was associated with an increase in the levels of two hormones, GLP-1 and YY, which play a role in hunger control, insulin sensitivity, and blood sugar control after meals.

According to the researchers, “daily almond snacking not only helps maintain gut homeostasis but also may alter the metabolic state and improve metabolic health.” 

Keep this in mind the next time you go grocery shopping.

When talking about infertility (sidenote: Infertility Disorder of the male or female reproductive system defined by the inability to achieve pregnancy after 12 months or more of regular unprotected sexual intercourse. https://www.who.int/news-room/fact-sheets/detail/infertility
  ) and ART (assisted reproductive technology), we often think of a journey filled with hope, expectation... and sometimes disappointment. Among the proposed techniques, frozen embryo transfer consists of placing in the uterus an embryo previously conceived in the laboratory through in vitro fertilization (IVF) (sidenote: In vitro fertilization (IVF) A medical assistance technique for procreation where fertilization takes place in the laboratory, in a test tube (“in vitro”), and not in the woman’s uterus: eggs retrieved from the woman after hormonal stimulation are placed in a nutrient solution with sperm collected from the man. The embryos thus conceived in the laboratory will then be transferred to the future mother’s uterus via the vagina. If an embryo implants, the pregnancy begins. https://www.service-public.fr/particuliers/vosdroits/F31462
https://medclinics.com/fr/fiv/
https://www.fiv.fr/fecondation-fiv/ ) , then frozen and subsequently transferred.

The aim? To achieve embryo implantation, thus initiating the eagerly awaited pregnancy. However, in reality, it’s not automatic: only 41% of egg retrievals result in pregnancy in women under 35.

+52% pregnancies with Lactobacilli

In this context, every little bit helps. And it seems that help might come from the microbiota, already involved in female and male infertility and in miscarriages. Could it also promote embryo implantation in cases of ART? A study conducted in the United States focused on 87 women who underwent frozen embryo transfer. It analyzed their vaginal microbiota at the time of transfer to see if it influenced the outcomes.

Result: among women whose vaginas were largely dominated by lactobacilli, particularly Lactobacillus crispatus or L. gasseri species, chances of pregnancy were 52% higher! Two-thirds of the women who became pregnant after embryo transfer had more than 80% lactobacilli in their vaginas.

Conversely, women whose microbiota hosted more opportunistic bacteria like Enterobacteriaceae or Streptococcus were less likely to become pregnant. However, neither the richness nor the diversity of the flora was associated with ART success: it is the type of bacteria that makes the difference.

An explanation for ethnic disparities?

Another interesting point addressed by the study: ethnic disparities. The authors made sure to include Hispanic women, who represent 19% of the US population but are often missing from studies.

The results show they had lower pregnancy rates. And their vaginal microbiota is less often dominated by beneficial Lactobacillus compared with non-Hispanic white women. A link worth exploring, which could partly explain lower rates of successful frozen embryo transfer in the Hispanic community.

Glycans are sugar molecules located on the surface of cells and in human secretions (including cervicovaginal fluid). They are specifically recognized by antibodies, lectins (sidenote: Lectins The term lectin (from the Latin word lectus, “chosen”) was coined by William C. Boyd and Elizabeth Shapeleigh in 1954 to refer to a heterogeneous class of (glyco)proteins, mainly of plant origin. Despite their wide range of physicochemical properties and biological activities, lectins share a common characteristic that is responsible for their various biological, biochemical, and immunochemical effects: they bind with high affinity and specificity to mono- and oligosaccharides of complex carbohydrates (including glycans) in solutions, on cell surfaces, subcellular organelles, and tissue sections. Source : Vierbuchen, M. (1991). Lectin Receptors. In: Seifert, G. (eds) Cell Receptors. Current Topics in Pathology, vol 83. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-75515-6_10 ) , and carbohydrate binding proteins. For example, in the vagina, host glycans modulate microbial colonization, acting as both binding and adhesion sites and sources of nutrients.

To better understand the interactions between these human glycans and the main pathogenic vaginal bacteria implicated in reproductive health, the researchers constructed glycan “chips” and tested the adhesion of bacteria in vitro under acidic (pH = 4) to neutral (pH = 7) conditions to reflect the reality of vaginal pH gradients observed in women.

A range of glycan-binding proteins

The results showed that the various bacteria tested could bind, to varying degrees, to several types of glycan. Moreover, according to previous work by the same team, pathogens appear to have a broader range of proteins that bind to these glycans than commensal species.

Some of the bonds are shared by different bacteria: with the exception of a few glycans, the binding profiles of the commensal bacteria Lactobacillus crispatus and L. iners and those of potentially pathogenic bacteria such as Gardnerella vaginalis and Streptococcus agalactiae overlapped, which could reflect competitive binding.

In contrast, other bonds are very specific: Fusobacterium nucleatum shows a preference for galactose-terminating glycans, while S. agalactiae is one of the few bacteria to bind to hyaluronic acid-terminating glycans.

Towards glycan-based therapies?

These results pave the way for the development of glycan-based therapies which block the adhesion of pathogens or promote colonization by probiotics. The aim is to one day reduce the incidence of bacterial vaginosis, preterm birth, and associated neonatal complications.

In assisted reproductive technology (ART), embryo implantation failures remain difficult to explain, probably because they involve multiple factors. Among these, a vaginal microbiota dominated by Lactobacillus seems to enhance the success of embryo transfers. However, results can sometimes be contradictory, and the ethnic origin of women is rarely considered.

A prospective single-site observational study¹ (Phoenix, USA) has therefore analyzed the vaginal microbiota of 87 American women during frozen embryo transfers, including 15 women of Hispanic origin. Its goal: to better understand the impact of vaginal flora on pregnancy rates after frozen embryo transfer, highlighting the protective role of Lactobacillus, while considering ethnic diversity.

More Lactobacillus, more pregnancies

Of the 55 patients who became pregnant, two-thirds (67%, or 37 women) exhibited a microbiota dominated by Lactobacillus at the time of insemination. These women had a 52% higher chance of becoming pregnant compared with those whose flora was not dominated by lactobacilli. Patients who did not become pregnant had more opportunistic pathogens, notably species of Enterobacteriaceae and Streptococcus.

In contrast, the richness or diversity of the vaginal flora was unrelated to ART outcome. Thus, the vaginal microbiota appears to interact with female fertility and the outcome of frozen embryo transfer: vaginal microbiomes dominated by Lactobacillus, especially those where the species L. crispatus or L. gasseri are prevalent, are positively associated with pregnancy. 

Explaining ethnic disparities?

The study also examined ethnic disparities. Hispanic women, who made up 18.3% of the cohort’s women (and about 19% of the US population), had lower clinical pregnancy rates following embryo transfer, a trend also observed nationally.

Moreover, a smaller proportion of them had a vaginal microbiota dominated by lactobacilli (compared with non-Hispanic white women), an observation already reported in previous studies. Could this lower prevalence of Lactobacillus dominance among Hispanic women partly explain the lower success of embryo transfer in this population? That is indeed the researchers’ hypothesis.

With 1.1 million deaths each year, preterm birth is the leading cause of death among young children under the age of five. Sadly, misfortune never comes alone, the risk of giving birth to another preterm baby being high, ranging from 15% to over 50%. The earlier in the pregnancy the previous preterm birth (sidenote: Preterm bitrh Babies born alive before 37 weeks of pregnancy are completed. There are sub-categories of preterm birth, based on gestational age: - Extremely preterm (less than 28 weeks). - Very preterm (28 to less than 32 weeks). - Moderate to late preterm (32 to 37 weeks). https://www.who.int/news-room/fact-sheets/detail/preterm-birth ) , the higher the risk of recurrence.

Medical science is searching for solutions, but a lack of knowledge about what causes these recurrences, which are probably multifactorial, limits the effectiveness of the treatments on offer (progesterone (sidenote: Progesterone Female sex hormone secreted after ovulation and during pregnancy. ) , cervical cerclage (sidenote: Cervical cerclage A surgical procedure performed during pregnancy whereby a thread is placed around the cervix when there is a risk it may open too easily. ) ,etc.). Could the solution lie partly in the vaginal flora?

This was the hypothesis of a group of researchers who followed 152 pregnant Chinese women at high risk of miscarriage, and their vaginal microbiota, sampled with a cotton swab during early pregnancy (before 16 weeks) and then between 16 and 24 weeks.

Risk linked to L. Iners.

Follow-up of these women showed that a vaginal microbiota dominated by Lactobacillus iners before 16 weeks of gestation is associated with an increased risk of premature birth. What explains this link? According to the authors, a vaginal flora dominated by L. iners is less stable than one dominated by L. crispatus: the former tends to evolve easily into a flora in which beneficial strains of Lactobacillus no longer reign supreme. In other words, it is less effective at keeping pathogenic bacteria at bay, as has already been shown in the case of Group B Streptococcus.

However, between 16 and 24 weeks of gestation the link between L. iners and preterm birth is no longer evident, highlighting that early pregnancy is the crucial period, perhaps one day even for intervention on the vaginal microbiota to reduce the risk of recurrent preterm birth. It should be noted that this type of intervention is no longer the stuff of science fiction: one 30-year-old mother who suffered a series of miscarriages after her first child was able to become a mother again after a vaginal microbiota transplant.

Vaginal microbiota is a complex ecosystem of bacteria inhabiting the vagina which plays a crucial role in women’s health, including during pregnancy. As an example, a higher concentration of lactobacilli appears to reduce the risk of miscarriage.

Among the various lactobacilli in the vaginal flora, Lactobacillus iners is particularly interesting as this bacterium is found in both healthy and pathological microbiota, raising questions about its exact role. A study conducted on 91 Chinese women in the third trimester of pregnancy provides new insights.

Higher levels of L. iners in healthy women

The study shows that one in two healthy women harbors a vaginal flora dominated by L. iners, whereas fewer than one in three women in the “unhealthy” group (gestational diabetes (sidenote: Gestational diabetes Gestational diabetes can develop during pregnancy in women who don't already have diabetes, usually around the 24th week. Testing is typically done between 24 and 28 weeks. It occurs when the body can't produce enough insulin during pregnancy—a hormone that allows blood sugar (glucose) to enter the cells to be used for energy. As a result, blood sugar levels (glycemia) become higher than normal. Every year, 5% to 9% of pregnancies in the U.S. are affected by gestational diabetes. Proper management of gestational diabetes helps ensure a healthy pregnancy and a healthy baby. CDC ) , pregnancy complications, etc.) have this type of microbiota. Conversely, a flora dominated by L. crispatus is more frequent among expectant mothers with health issues.

For example, this type of microbiota is present in 57% of women with gestational diabetes.

Could the higher frequency and abundance of L. iners explain the good health of pregnant women? Researchers believe this could be true. This is because a higher presence of L. iners means an enhanced production of beneficial microbial molecules by this bacterium. This includes an increased biosynthesis of a compound with the intimidating name “tetrahydrofolate” which helps maintain moderate inflammation in late pregnancy.

Different strains of L. iners

However, not all L. iners strains are the same. Among the seven strains identified in pregnant women, three strains associated with bacterial vaginosis (sidenote: Bacterial vaginosis Bacterial vaginosis (BV) is a type of vaginal inflammation caused by an imbalance of the bacterial species that are normally present in the vagina. ) were particularly adept at forming feared biofilms, which serve as shelters where pathogens can multiply. Four other strains (some associated with vaginosis, others not) appeared capable of inhibiting the growth of the pathogen Gardnerella vaginalis. In short, each L. iners strain has its own characteristics—and likely several tricks up its “bacterial” sleeve. But some strains could help maintain the stability of the vaginal ecosystem in pregnant women.