Necrotizing enterocolitis (NEC) is a serious and sudden necroinflammatory complication in preterm infants. Previous studies suggest an involvement of the gut microbiota in its occurrence, while others point to a possible involvement of certain viruses. However, the gut virome of preterm infants remained poorly understood until now. An American team therefore monitored the development of the virome in preterm infants over time in order to identify the factors that could influence the development of NEC.

Convergence of viromes 10 days before disease onset

In this longitudinal metagenomic study, the gut viromes of 23 preterm infants were analyzed by next-generation sequencing during their first 11 weeks of life, i.e. between 25 and 36 weeks postmenstrual age. Nine of these children developed NEC at a median postmenstrual age (sidenote: Postmenstrual age age corresponding to the number of weeks of gestation at birth plus the postnatal age. ) of around 31 weeks; four did not survive.

The results show that the gut virome of preterm infants displays high inter- and intra-individual variation over time. This observation is identical whether or not the infants developed NEC. On the other hand, a particularly interesting result was that the gut viromes of infants who developed NEC began to converge in terms of beta diversity (sidenote: β diversity A measure indicating the species diversity between samples, it allows to assess the variability of microbiota diversity between subjects. Hamady M, Lozupone C, Knight R. Fast UniFrac: facilitating high-throughput phylogenetic analyses of microbial communities including analysis of pyrosequencing and PhyloChip data. ISME J. 2010;4:17-27. https://www.nature.com/articles/ismej20099 ) 10 days before disease onset. This convergence was expressed by enrichment of specific viruses and the loss of other viruses.
With respect to bacteria, bacterial beta diversity in these infants was stable during the 25 days preceding NEC onset. However, over this period, the abundance of Gammaproteobacteria, Bacilli, Enterococcaceae, Enterobacteriaceae and Veillonellaceae differed between case samples versus control samples.

Identifying at-risk children

There are therefore viral signatures associated with specific virus-bacteria interactions which appear around ten days before NEC onset. This suggests the involvement of the gut virome in preterm infants in the pathogenesis of this complication. As geography is a factor that can influence the microbiome and the virome, these results obtained in a single hospital in the United States will need to be confirmed in other populations. Nevertheless, they open up the possibility of early identification of infants at increased risk of developing NEC.

Urinary tract infections (UTIs) are among the most common bacterial infections worldwide. They occur when bacteria from the skin or rectum enter the urethra, infecting the urinary tract.^1,2 A recent US study followed thirty women suffering from UTIs and undergoing antibiotic treatment for one year. The findings are clear: women with UTIs are caught in a vicious circle. Antibiotics prescribed to relieve the current crisis may set the stage for the next one.

It begins in the gut microbiota

It all starts in the gut. Bacteria called Escherichia coli travel from the anus up the vulva into the urinary tract. So far nothing unusual, since the same phenomenon is observed in women not prone to such infections. Usually, the immune system takes care of eliminating unwanted intruders. However, in women with chronic urinary tract infections, the immune system is not up to scratch. This is probably due to repeated antibiotic treatments that partly eliminate the bacteria responsible for regulating our immunity via small molecules produced in the gut which then pass into the bloodstream.

As a direct result, E. coli triggers a new urinary tract infection and the doctor, at a loss, prescribes a further antibiotic treatment. And here we go again, since this new treatment will certainly eliminate the bacteria in the bladder, but not the reservoir of comfortable E. coli in the gut.
What’s worse, the treatment may further disrupt friendly bacteria in the gut microbiota that help regulate the immune system so that it can prevent E. coli from reaching the bladder.

Changing strategy

The bottom line is that 20%-30% of women will quickly see their UTI return, not to mention the development of antibiotic resistance, which will complicate the treatment of any new crisis. How can the vicious circle be stopped? Perhaps by changing strategy. Instead of trying to eliminate undesirable bacteria regardless of any long-term collateral damage to the beneficial bacteria that regulate our immunity, another option is to pamper the bacteria that ensure a balanced gut microbiota. The basis for this idea is that women prone to urinary tract infections have a gut microbiota that is less diverse and less rich in friendly bacteria.

Hence the authors’ suggestion to focus on microbiota therapies to restore bacterial communities in infection-prone women.

The second most common cancer in men worldwide, prostate cancer is also the fifth deadliest cancer with more than 375,000 deaths in 2020². Its course, often slow, however varies significantly from one patient to another. The degree of aggressiveness of the tumor (or "grade") therefore plays a major role in the treatment decision.

Treatment can also be deferred in favor of monitoring if the cancer seems to be progressing little. To determine this grade and monitor its progession, doctors must resort to biopsies, which are invasive examinations. New ways of detecting aggressive forms of prostate cancer, ideally through urine tests, are therefore eagerly awaited.

Urine and prostate microbiota under the microscope

It is already known that bacteria play a role in several types of cancer. Recent studies also showed that prostate cancer was associated with a particular urinary microbial profile. Finally, a recent publication suggests that the gut microbiota could be used as a marker of progression of this cancer.

English researchers therefore analyzed more than 600 samples of urine, of secretions and of prostate tissue from men stratified according to their risk of disease progression.
The objective was twofold:

• to study the urinary and prostatic microbiota of the subjects
• and to see if the bacteria that compose them were linked to tumor aggressiveness in the affected patients.

Previously unknown bacteria: new weapons against prostate cancer? 

The researchers were not only able to show a link between the presence of bacteria in urine and a higher risk of prostate cancer, but also identified four previously unknown bacteria for the first time. Additionally, five specific bacterial genera, three of which include these newcomers, were associated with a 2.6-fold increased risk of rapid disease progression. They could therefore serve as potential prognostic markers for the progression of prostate cancer.

A team of researchers recently investigated the link between fecal and salivary microbiota and the development of pancreatic ductal adenocarcinoma (PD), the most common form of pancreatic cancer.

To do this, 2 cohorts of patients (136 Spanish patients and 76 German patients) were recruited and their saliva, stool and pancreatic tissue samples (tumor or healthy) were collected in order to perform analyses on the bacterial species that compose them.

Fecal microbiota, a new ally in pancreatic cancer detection?

While the salivary analyses did not provide much information, the analysis of the fecal microbiota proved to be particularly instructive and... hopeful. Indeed, 27 disease-specific bacterial species were identified and led to the construction of a statistical model for the identification of pancreatic cancer patients, regardless of the severity of their disease. The accuracy of detection was further enhanced by combining this model with the use of an existing marker used in pancreatic cancer (CA 19-9 carbohydrate antigen), but with low sensitivity and specificity.)

The researchers then confirmed their detection model on the second cohort of 76 German patients, as well as on 5792 patients from 18 different countries suffering from various pathologies (PA, obesity, diabetes, colorectal cancer...): in both cases, the signatures of the intestinal microbiota specific to PA are accurately detected. 

Vaginal dryness, pain, itching: postmenopause often comes with genitourinary symptoms. Vaginal estradiol or a moisturizing cream are frequently prescribed to relieve these symptoms, but the impact of these treatments on the vaginal microenvironment is poorly understood.

A comparative study

In 2016-2017, 302 postmenopausal women (average age 64) with moderate to severe vulvovaginal discomfort took part in the MsFLASH Vaginal Health Trial, a multicenter double-blind randomized clinical trial.

Should these changes be interpreted as a beneficial effect on the vaginal environment beyond the mere improvement of symptoms? This is what the researchers sought to find out via a post-hoc analysis of a sub-group of 144 postmenopausal women.

Towards a healthier vaginal microbiota?

At 12 weeks, 80% of women in the estradiol group had vaginal bacterial communities dominated by Lactobacillus and Bifidobacterium, compared to only 36% in the moisturizer group and 26% in the placebo group.
Another change observed in the estradiol group was a change in the composition of vaginal fluid metabolites (significant changes for more than half of the 171 metabolites tested), including an increase in lactate, most certainly contributing to the additional decrease in pH in this group.
The effect of estradiol was more pronounced in women who initially had a very diverse vaginal microbiota (considered less healthy), a high vaginal pH, and a low VMI. Estradiol may therefore stimulate the metabolic activity of beneficial lactic acid-producing bacteria, such as lactobacilli and bifidobacteria.

Multiple findings

• The use of vaginal estradiol tablets appears to result in profound changes to the vaginal microbiota and metabolome.
• The benefits of the low pH moisturizer and the double placebo (lubricating effect) are limited to symptoms only.They show no significant impact on the vaginal microbiota or metabolome, despite the decrease in vaginal pH they bring about. 
• This study shows that an identical reduction in pH following two different types of treatment does not necessarily reflect the same underlying biological effect, and that reducing the vaginal pH is not enough to modify the vaginal microbiota in postmenopausal women. According to the authors, this puts the value of pH-balanced gels into perspective.

Progress in terms of prevention, diagnosis and treatment has had little actual effect: coronary artery disease remains one of the world’s leading causes of morbidity and mortality. The disease involves a complex physiological process with multiple interacting risk factors. Of these many factors, several circulating metabolites derived from the gut microbiota are now known to be linked to cardiovascular disease. Hence this study of the multifactorial nature of coronary artery disease, specifically investigating the gut microbiota and serum metabolites in 199 Israeli patients with acute coronary syndrome (ACS).

When an absence of metabolites signals the disease

The microbial signatures (around twenty depleted or enriched bacteria) and metabolomic signatures (hundreds of disrupted metabolites) were different in the ACS patients compared to the 970 controls. Some forms of intestinal dysbiosis had already been reported, such as a relative depletion in butyrate-producing bacteria (sidenote: butyrate-producing bacteria Clostridium, Anaerostipes hadrus, Streptococcus thermophilus, and Blautia ) , and an abundance of Odoribacter splanchnicus and Escherichia coli. But the researchers also found a lower quantity of a previously unknown bacterial species of the Clostridiaceae family: SGB 4712. This depletion was also found in a geographically distinct cohort (MetaCardis, Northern Europe), confirming the robustness of their observation. The presence of SGB 4712 is therefore negatively associated with cardiotoxic metabolites and positively linked to other protective ones. This suggests that SGB 4712 could play a protective role in the development of coronary artery disease, via a range of circulating blood metabolites. Or possible new therapeutic targets.

The protective role of the microbiota in coronary artery disease

Second finding: the metabolic signatures of the ACS patients were specific to each patient.

• Among these patients, the depletion of certain bacteria was primarily linked to the microbiome and diet, suggesting their early involvement in coronary artery disease via a deficiency of protective metabolites (metabolic syndrome).
• This is opposed to traditional risk factors (sidenote: Traditional cardiovascular disease risk factors age, sex, anthropometric data, blood pressure, smoking, and diabetes. ) and genetics, which come into play at a later stage in ACS and cardiovascular accidents.

According to the authors, the microbiota could play a protective role in coronary disease, resulting in a different disease experience for patients with similar clinical profiles.

What has the national grant allowed to discover in your microbiota research area?

The National grant allows me to explore the research field of my interest and develop my independent research projects. I was involved in multiple projects and Biocodex Microbiota Foundation USA grant was acknowledged in 8 of my publications.

What are the consequences for the patient?

My research grant was focused on animal experiments. We discovered that gut microbiota not only plays an important role in blood pressure regulation, but also contributes to the modulation of antihypertensive drugs' efficacy. This new concept may provoke discussion on the management of resistant hypertension.

BMI 22.31

What has the national grant allowed to discover in your microbiota research area?

National Grant allowed me to explore how recycling of polyphenols can modulate the structure and function of gut microbiota, which not only impact the systemic bioavailability of these compounds but also generate microbial metabolites beneficial for humans health and alleviation of various gut diseases/disorders.

What are the consequences for the patient?

Our research indicates the mechanism of benefits of polyphenol-rich diet despite their low systemic bioavailability lies in their bidirectional interactions with gut microbiota which is facilitated by their hepato-enteric and entero-enteric recycling phenomenon. It supports the consumption of flavonoids or polyphenol rich foods and dietary supplement not just for their antioxidant effects as has been marketed but also for their positive impact on maintaining healthy gut microbiota to build resilience against toxins.

BMI 22.32

What has the national grant allowed to discover in your microbiota research area?

My project involves isolating and characterizing Fusobacterium strains from colon cancer biopsies. It’s a truly translational project that appeals to me as a physician scientist because it allows me to work directly with patient samples to investigate an important observation that the oral microbe Fusobacterium nucleatum is enriched in the microbiome of many colon cancer patients. I had some exciting pilot data but needed additional research funds and technical support to expand the project. The grant has allowed us to complete 16S rRNA sequencing of our colon cancer surgical biopsy cohort, giving us a broad view of the bacterial composition of the tumor microbiome. We are now analyzing these data in the context of specific patient characteristics (e.g. tumor stage, tumor location, patient demographics). In parallel, we are isolating individual Fusobacterium strains and performing whole genome sequencing and testing these strains in our mouse models, providing mechanistic data about how these organisms may contribute to disease in the colon. Our preliminary data thus far have highlighted the genomic diversity of F. nucleatum and strain-specific phenotypes in mouse models of CRC (these data recently described in mBio¹), and we have some exciting preliminary data demonstrating a potential novel pro-carcinogenic effect of other Fusobacterium species.2

What are the consequences for the patient?

Our in-depth analysis of this CRC cohort will provide higher resolution data about the tumor microbiome, because we are combining sequencing, culture, and in vivo models to investigate commensal organisms to the subspecies and strain level in a way that has not previously been done for Fusobacterium nucleatum. Ultimately, our hope is that a deeper understanding of the cancer-associated microbiota will provide opportunities for development of novel preventative and therapeutic interventions, and to allow a more personalized medicine approach to treatment.

BMI 22.30

What has the national grant allowed to discover in your microbiota research area?

The human gut microbiome is now widely recognized as a key contributor to health but the presence of a proximal small intestinal or duodenal microbiome remains largely understudied. With the support of the national grant, we studied the duodenal mucosa-associated and luminal microbiome in healthy volunteers and functional dyspepsia patients. A link between specific bacteria and symptoms was found in patients, and bacterial changes on proton pump inhibitors (PPI) were associated with potential inadvertent effects of these drugs in healthy volunteers. 

What are the consequences for the patient? 

The discovery of potential microbial biomarkers and therapeutic targets may ultimately contribute to the diagnosis and innovative treatments for functional dyspepsia. Moreover, microbial changes on PPI provide additional arguments not to initiate or continue PPI without a clear indication and to reduce inappropriate prescribing.