C-section, infant formula and antibiotics are regularly associated with increased risks of obesity, allergy or even diabetes mellitus. What do they have in common? They all seem to disrupt the bacterial colonization of the gastrointestinal tract that started at birth. But we still do not know the individual effects of each of these parameters, as well as its combined impact, on the structure and composition of the gut microbiota. To try and find an answer, researchers analyzed the bacterial flora of 120 six-week old babies, divided into groups based on the type of delivery, type of breastfeeding (exclusive or mixed feeding) and exposure to antibiotics since birth.

Low content of bifidobacteria

Compared to children born vaginally, the gut microbiota of newborns born through c-section had significantly less bifidobacteria (which promote good intestinal and immune health) and an increased content of two types of potentially harmful bacteria. The gut microbiota of breastfed children was, however, approximately the same as that of babies who alternated between breast milk and formula. But when combining these two variables, the researchers observed that only children born through C-section were impacted by the type of breastfeeding. What if the microbiota of these babies was altered by maternal milk? When testing this hypothesis, the researchers observed that the microbiota of babies born through C-section and exclusively breastfed was very close to that of babies born vaginally. Exposure to antibiotics, however, had no impact on the gut flora. The authors believe this was probably because treatments were administered for a short period of time and at low doses.

C-section + maternal milk = healthy microbiota

This study provides new insights into a controversial issue, since only the mode of delivery seems to have an impact on the structure and composition of newborns’ gut microbiota. It also shows that in case of c-section, the flora can partly be restored by exclusive breastfeeding, thus unveiling new benefits of this practice which is strongly recommended by the World’s Health Organization.

Despite the positive results obtained with fecal microbiota transplants (FMT) as a first-line treatment for recurrent Clostridium difficile infections (rCDI), 8 to 50% of patients relapse. Recent works have shown the potential influence of bacteriophages–a virus that infects bacteria within the gut microbiota–on the success rate of fecal transplants. A Canadian team thus studied the impact of bacteriophage populations in donors and patients with rCDI treated with FMT via colonoscopy.

Impact of FMT on bacteriophages

Unsurprisingly, all 19 recipients from this trial had a less diversified gut microbiota than the 7 donors. The diversity of their bacteriophages was greater than that of donors and of the 96 control subjects. This was potentially due the administration of vancomycin in the 24 hours before the transplant, which could trigger the induction of phages. The FMT, which was effective from the first administration in 12 patients, led to a reduction of this increased diversity. For the 7 patients who received a second FMT, bacteriophage diversity was only reduced on the second attempt.

Importance of donors’ profile

On the bacterial front, recipients’ profile became more similar to the donors’ after a successful transplant: increased levels of Bacteroidetes and Firmicutes, decreased levels of Proteobacteria, which were prevalent until then (mainly species from the Klebsiella and Escherichia genera). Nevertheless, no difference was observed between patients who had a positive response after the first transplant and those who did not. On the contrary, donors’ bacteriophages seem to be correlated to the successful or failed outcome of the transplant: greater diversity as well as decreased relative abundance were associated to a successful FMT. But before using donors’ bacteriophage composition as a prognostic factor for FMT in the treatment of rCDI, the researchers call for revised research methods into this facet of the gut flora which is still largely unknown. They believe these results are probably only the “tip of the iceberg”.

Explain fecal transplantation to your patients with this dedicated content: 

How did some species of frogs resist to the chytridiomycosis outbreak, a fungal infection which has decimated amphibian populations around the world? Could it be thanks to the presence, within their skin microbiota, of bacteria able to fight against the fungus Batrachochytrium dendrobatidis, which is responsible for this disease?

A therapeutic lead against aspergillosis?

To know for certain, researchers isolated several bacterial strains colonizing the skin of 7 species of frogs living in Panama, a country particularly affected by the epidemic. They then decided to investigate whether the bacterium B. dendrobatidis could stop the fungus development and if it could block the growth of Aspergillus fumigatus, a fungus causing over 80% of human aspergillosis. Their aim was to develop alternative therapies whose mechanisms of action would be different from that of standard antifungal agents.

Saving own skin ... thanks to the skin!

The bacterium Pseudomonas cichorii, which is present on the skin of frogs, holds first place as most potent antifungal thanks to the production of two active compounds, one of which has shown, in laboratory tests, a strong capacity to stop the growth of pathogenic fungi B. dendrobatidis and A. fumigatus. This finding still has to be confirmed in living organisms in order to prove that Pseudomonas cichorii truly prevents the development of the resulting diseases. Panamanian frogs could thus have escaped a massive extinction caused by a killer fungus thanks to their skin! Skin bacteria responsible for their survival could well be used to develop new natural remedies against human aspergillosis.

Breast milk is not sterile and the flora it hosts contributes to the development of newborns’ gut microbiota. But are all breast milk feeding techniques equally effective? To find out, an international team analyzed the composition of breast milk microbiota, either pumped or given directly from the breast, in 393 new mothers.

Impact of using a breast pump

The microbial composition of 393 breast milk samples, collected on average 3-4 months after birth, was matched to the breastfeeding mode of each mother and specific parameters (BMI, parity, delivery mode...) using several statistical methods. Bifidobacterium spp., bacteria involved in the maturation of the child’s immune system, were more abundant in the milk when it was given directly from the breast. Independently of other factors traditionally considered (mother BMI, delivery mode...), expressed breast milk feeding (defined as at least one feed with expressed milk in the previous two weeks), and especially with an electric breast pump, significantly reduced abundance and diversity of the milk’s microbiota. It also induced an increase in several families such as Enterobacteriaceae, Enterococcaceae, Stenotrophomonas and Pseudomonadaceae, of which some species are potential opportunistic bacteria. This observation suggests that environmental factors impact indirect breastfeeding.

Other factors to be considered

Results also indicate that in case of direct breastfeeding, the newborn itself regurgitates and contaminates the milk with its own oral microbiota (“retrograde inoculation” hypothesis), in a gender-specific manner. This is an additional argument supporting the idea of a shared mother-child contamination. Similarly, maternal factors could have an impact: ethnicity, BMI (able to modulate, among others, the amounts of fatty acids, hormones or oligosaccharides in the milk), delivery via C section (leading to decreased bacterial diversity and abundance in the milk), smoking, primiparity or multiparity, existence of an atopic field. And let’s not forget translocation of gut microorganisms towards the mammary glands, through the “entero-mammary pathway”. These findings could lead to potential avenues to improve milk microbiota, and consequently newborns’ intestinal flora, and implement prevention strategies for chronic diseases from an early age (allergies, respiratory infections. asthma...).

Many studies now confirm the existence of a correlation between gut dysbiosis (sidenote: Dysbiosis Generally defined as an alteration in the composition and function of the microbiota caused by a combination of environmental and individual-specific factors. Levy M, Kolodziejczyk AA, Thaiss CA, et al. Dysbiosis and the immune system. Nat Rev Immunol. 2017;17(4):219-232.   ) and schizophrenia based on known factors: the risk of developing the disease is 10 to 20 times higher when there was a prenatal infection; frequent gastrointestinal disorders associated with a dysbiosis in schizophrenic patients; as well as disruptions in the neurological, immune and hormonal systems, whose maturation is closely linked to the gut flora. Chinese researchers have thus compared the microbiota of healthy individuals to that of schizophrenic patients, before transferring imbalanced “schizophrenic” flora into microbiota-free mice.

The microbiota is related to the disease and its severity

The microbiota of schizophrenic patients is not only less abundant and less diverse, but there is also a predominance of 23 species (out of the 77 that have been identified); and the remaining 54 are underrepresented. This dysbiosis is specific to schizophrenia according to the authors, who have also identified a bacterial signature made up by 5 families. This signature is able to discriminate between healthy individuals and schizophrenic patients and it is different from the signature found in other psychiatric disorders (such as depression). Moreover, two large bacterial groups could be specifically correlated to the severity of schizophrenic symptoms.

Microbiota transplant and disease onset

Schizophrenia seems to be transferable to healthy microbiota-free mice through a gut microbiota transplant: the bacterial signature of human donors is found in recipient rodents who started to present behavior proper to schizophrenia: hyperactivity, decreased anxiety and depression. Abnormal variations in some neurotransmitter levels (chemical substances that allow neurons to send messages) were also observed, thus indicating that the gut-brain communication is altered. Researchers concluded that gut dysbiosis could play a role in the development of schizophrenia through this pathway. This discovery opens the way to new potential diagnostic and therapeutic strategies.

Crohn’s disease is an unpredictable and chronic disease, which progresses very variably from a patient to another. Although the causes of this inflammatory disease are not well known, it has been observed that patients’ gut microbiota seems to be less balanced than that of healthy subjects. But is it a cause of the disease, or a simple adaptation of the microbiota to an environment that has become inflammatory?

Two-year observational study

To get a clearer picture, a team of Israeli and American researchers monitored the microbiota of 45 patients in the remission phase of the disease. During this prospective observational study, the following tests were performed: analysis of gut microbiota, measurement of C-reactive protein (every 3 months) and fecal calprotectin levels, as well as endoscopic assessments (every 6 months). Results were compared to those of 17 patients in the inflammatory phase of the disease and to those of 22 control subjects. Objective: identifying whether flares are preceded by gut microbiota disruptions. To optimize the analytical process, the researchers used machine learning, a computer-based technology where analytical models are developed based on compiled data instead of prior programming.

Flares and microbiota instability

Results confirm that patients with Crohn’s disease have generally less abundant and more unbalanced microbiota (higher dysbiosis index) than healthy subjects. They mainly underline that in 27 out of the 45 patients who had a flare-up in the two-year follow-up period, they observed that this inflammatory phase was preceded by a significant decrease in the levels of some bacteria (Christensenellaceae and S24.7 families) and increase in others (Gemellaceae) compared to patients who remained in remission. Moreover, patients whose gut microbiota is more unstable in the resting phase of the disease are 11 times more likely to experiment an upcoming flare. Changes in the relative abundance of the three aforementioned taxa and global instability of the gut microbiota seem to precede flare‑ups, thus indicating that the gastrointestinal flora plays a role in flare pathogenesis. Despite the bias associated to machine learning (excessive individual variability compared to clinical factors), these results open the way to future tailored therapeutic options which could predict–and maybe one day prevent–upcoming flare-ups.

Diabetes mellitus prevention through regulation of blood sugar levels is mainly based on a diet containing less calories and less sugar. However, it seems that postprandial blood glucose levels (following food intake) do not only depend on the composition of ingested food: it varies from person to person based on individual parameters (physiological, genetic, or related to the gut microbiota).

With or without diabetes, all investigated!

According to an Israeli study conducted in 2015 with people with a predisposition to diabetes (overweight or obese), dietary interventions adapted to individual data (including gut flora) lower glucose levels more effectively than the standard model, which is exclusively based on low calorie and glucose intake. What about people without diabetes? American researchers from the Mayo Clinic tested the tailored model on 327 healthy adults from the Midwest region. While retaining their dietary habits (except breakfast which was normalized) participants had to wear a glucose meter in order to permanently monitor their blood glucose levels and a food tracking app recorded the nutritional values of their meals. All data were then compared to the predictions obtained through the tailored model and the standard model.

Microbiota and control of blood glucose levels

To some extent, the results of the Israeli study were confirmed: the same food can trigger very different glycemic responses from one person to another, while the response from the same individual over time remains relatively constant. Moreover, postprandial glucose levels predicted by the tailored model were closer to the data reported by participants than those predicted by the standard model. This difference could partly be explained by the composition of our gut microbiota, which could play a role in keeping glucose at normal levels (glucose homeostasis). All these findings tend to support a tailored dietary approach to prevent diseases associated with abnormally high blood sugar levels (hyperglycemia).

“One of the greatest threats against global health, food safety, and development.”

This is how the WHO characterizes antibiotic resistance, which leads to longer hospital stays, higher medical expenditure and increased mortality. Among potential solutions under investigation, fecal microbiota transplant (FMT) brings hope to the fight against multi-drug resistant bacteria but still raises questions regarding its safety, especially in immunocompromised patients.

10 immunocompromised patients were tested

A monocenter study was based on the retrospective analysis of 10 patients with blood disorders, undergoing a bone marrow transplant and who were (or had been) colonized by carbapenemase-producing or vancomycin-resistant bacteria which were classified as very high risk (eXDR, emerging extensively drug-resistant bacteria). The patients were about to receive an allogeneic (the donor is not the same person as the recipient) hematopoietic stem cell transplant (HSCT) following the treatment of their hematological cancer. The FMT was performed by enema or nasogastric tube, either before (for four patients) or after (for the remaining six who were still receiving immunosuppressants at the time of the procedure) the allograft.

Confirmed efficacy

In 7 out of 10 cases, investigators observed a significant decolonization of multi-drug resistant bacteria (3 successive bacterial cultures were negative). In 6 out of 10 patients, this decolonization persisted during the entire follow-up period (4-40 months). The three failures could be explained by methodological difficulties (antibiotics could not be suspended 72 hours after the FMT, the treatment period was too short, or the stool sample was too little...). Finally, when the first FMT was not able to eradicate multi-drug resistant bacteria, a second transplant turned out to be possible and effective in 2 out of 3 cases.

Proven safety

In all 10 patients, FMT was not associated to any major risk: one patient was constipated in the first days following the transplant; two others had transient, mild diarrhea. According to the researchers, none of the 3 reported deaths was attributable to the FMT. In two cases, the disease had progressed; and in the third case, the patient received two fecal transplants because of severe GVHD (sidenote: GVHD Graft-versus-host disease )  following the hematopoietic stem cell transplant, and the treatment with immunosuppressants led to the onset of a viral and fungal infection 6 months after the FMT. Consequently, in patients infected with multi-drug resistant bacteria, FMT seems to be an effective and safe solution, even in cases of severe immunosuppression.

Explain fecal transplantation to your patients with this dedicated content: 

About one third of the world’s annual plastic production ends up as land or marine pollutants, i.e. more than 100 million tons. Among this waste, plastic microparticles derived from cosmetics, petrochemical and clothing industries are a serious environmental issue. Smaller than 5 mm, they avoid filtration systems and are released into aquatic environments where it takes several centuries to break them down because of high salinity and low temperatures. As a result, they are colonized by all sorts of bacteria (sometimes toxic), before ending up in the stomach of sea organisms who are fooled by this false meal opportunity.

Singaporean coasts have been closely examined

Several studies have been carried out throughout the world to identify the nature of microorganisms proliferating on the surface of microplastics. What about Singapore? Do the waste polluting the most frequented beach waters have the same bacterial profile as that of immaculate beaches very rarely trampled by people? Two researchers for the University of Singapore decided to investigate. Fragments, fibers, foams, granulates, plastic films...: between April and July 2018, they collected and analyzed a total of 275 microplastic samples from three different beaches with different touristic affluence.

Human activity to blame

Not surprisingly, the more frequented the beach, the more polluted it was. But the nature of microplastics as well as that of bacterial species covering them were significantly different in each beach. This observation confirmed the impact of human activities on this pollution, also modulated by winds and tides. Good news: the ecosystem adapts to pollutants by promoting the development of bacterial species that are able to break them down. Bad news: it also allows for the emergence of pathogens, responsible for wound infections or gastrointestinal diseases. By inadvertently ingesting these microplastics, marine organisms could also trigger the accumulation and subsequent transfer of pathogenic agents into the food chain. The authors conclude that these two findings will have to be taken into account to meet the ecological and sanitary challenges caused by plastic pollution.