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.

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

The grant allowed us to investigate the relationship between the human gut microbiota composition and some pharmacokinetic (PK) markers of mycophenolic acid (MPA), an immunosuppressive drug largely used in solid organ transplantation, in a cohort of 100 stable renal transplant patients. A first screening analysis at the genus level revealed that 7 taxa were significantly correlated with the drug exposure as characterised by the MPA area under the concentration curve (AUC). Among these 7 genera, 4 showed a consistent difference in the low exposure group when compared to the medium & high exposure groups, which differences remained significant when correcting for false discovery rate. This correlation between MPA exposure and microbiota composition highlights a potential interaction. It suggests that either MPA impacts on the flora composition or, inversely, that the gut microbiota affects the drug enterohepatic recycling or, most probably, a combination of both. 

What are the consequences for the patient? 

The need of controlling immunosuppression is critical in transplanted patients to avoid inadequate exposure that can lead to inappropriate drug response, i.e. graft rejection or adverse drug reaction. As a chronic medication, identifying and understanding the factors affecting immunosuppressive drug PK are capital to master unanticipated deviations from therapeutic control. Our study constitutes a first step to the demonstration that the microbiota might contribute to the unexplained abnormalities reported in clinics and might further help the clinician to anticipate any potential PK deviance thereby, facilitating clinical management. 

BMI 22.37

Recommended by academic associations^2,3 and praised by the public, the Mediterranean diet (sidenote: Mediterranean diet Rich in fruit, vegetables, cereals, oilseeds (nuts) and fish, and low in red meat, saturated fats and dairy products. Lăcătușu CM, Grigorescu ED, Floria M, et al. The Mediterranean Diet: From an Environment-Driven Food Culture to an Emerging Medical Prescription. Int J Environ Res Public Health. 2019 Mar 15;16(6):942. ) has proven its effectiveness in reducing the risk of cardiovascular disease. But if it were more “vegetarian”, would the beneficial effects for our arteries be even greater? Recent studies suggest that by decreasing the proportion of animal proteins and fats in our diet in favor of vegetable equivalents (nuts, seeds, legumes, olive oil, etc.), the incidence of heart attacks, strokes, and death from cardiovascular disease would fall dramatically, 30%-40% less than with a “standard” diet.

Mankai and green tea: heart benefits of the Green-Med diet

Israeli researchers have just confirmed these results through their purpose-made Green-Med diet (sidenote: Green-Med “Green Mediterranean” diet ) , a “greener” version of the Mediterranean diet. The 300 individuals involved in the study all suffered from abdominal obesity and/or excess fat in the blood, and were therefore at cardiovascular risk. They followed either the Green-Med diet, a classic Mediterranean diet, or the standard “healthy” dietary guidance. All participants took part in moderate physical activity. The researchers also sought to explore the links between these diets and the gut microbiota, as well as their impact on weight loss and various determinants of cardiometabolic risk, such as waist circumference, blood pressure, and blood sugar control (sidenote: Insulin-resistance An altered response of cells to the action of insulin (a hormone that helps the body use sugar for energy), insulin resistance results in poor regulation of blood sugar levels. Sources
Inserm. La résistance à l’insuline, une histoire de communication. 2018. 
Centers for disease control and prevention. Diabetes - Resources and Publications -Glossary  ) .

The Mediterranean diets contained the same number of calories and were both supplemented with nuts (28 g per day). The Green-Med diet also included :

• green tea (3-4 cups per day)
• and Mankai (sidenote: Mankai Mankai, or Wolffia globosa, is an aquatic plant known for its nutritional qualities. It is rich in proteins (45% of dry weight), essential amino acids, omega-3 fatty acids, dietary fiber, polyphenols, and numerous micronutrients.
  Sela I, Yaskolka Meir A, Brandis A, et al. Wolffia globosa-Mankai Plant-Based Protein Contains Bioactive Vitamin B12 and Is Well Absorbed in Humans. Nutrients. 2020;12(10):3067. ) (100 g per day), an Asian plant rich in fiber and vegetable protein that can be used as a meat substitute.

These two foods also contain polyphenols known to influence fat metabolism⁴ and promote weight loss.

A modified microbiota with fewer microorganisms and amino acids linked to excess weight 

After six months, all three groups showed changes in their gut microbiota. However, the Green-Med diet was distinguished by several changes, particularly in rare, person-specific, and diet-influenced microorganism species. Specifically, it led to an increase in Prevotella, previously associated with vegetarian diets, and a decrease in Bifidobacteria, known to improve sugar metabolism and facilitate weight loss. Insulin resistance and the production and absorption by these microorganisms of certain amino acids involved in obesity were also reduced.

Green-Med, the champion of cardiovascular health

The results: the Green-Med diet topped the podium in terms of weight loss (-6.5% vs -5.4% for the Mediterranean diet and -1.6% for the standard diet). Green-Med also led to improvements in markers of cardiometabolic risk. According to the researchers, these benefits are at least in part related to Green-Med’s impact on the gut microbiota.

Yes, according to the work of a German-Spanish team published in the journal Gut in 2022. Based on the observation that alterations in the oral, fecal, and pancreatic microbiota are associated with an increased risk of pancreatic ductal adenocarcinoma (PDAC), the researchers sought to assess the potential of the salivary and fecal microbiota as diagnostic tools for the disease. The only PDAC marker approved by the FDA (sidenote: Food and Drug Administration US Federal Agency responsible for pharmacovigilance ) to date is carbohydrate antigen 19-9 (CA 19-9), which has limited sensitivity and specificity.

Diagnostic biomarkers identified via two cohorts

To evaluate the potential of the salivary and fecal microbiota as diagnostic biomarkers of PDAC, the researchers performed a metagenomic analysis (16S rRNA and shotgun sequencing) on fecal and saliva samples from two cohorts: 

• The first cohort (prediction cohort) included 136 Spanish patients divided into three groups (57 PDAC patients who had not started treatment, 29 patients with chronic pancreatitis, 50 controls);
• The second cohort (validation cohort) included 76 German patients (32 PDAC patients, 32 controls).

Lastly, the specificity of the model was validated against 5,792 gut metagenomic profiles from 25 public databases.

Fecal microbiota: superior diagnostic performance

The fecal microbiota performed better (AUROC=0.84) than the salivary microbiota in accurately identifying patients with PDAC based on a set of 27 species, regardless of the disease phase (Spanish prediction cohort). Accuracy increased (AUROC=0.94) when fecal metagenomic analyses were combined with the serum marker CA 19-9. Both models were validated against the independent German cohort (AUROC=0.83) and against the gut metagenomic profiles of 5,792 patients across 18 countries suffering from various diseases (PDAC, obesity, diabetes, colorectal cancer, etc.): in both cases, PDAC-specific fecal metagenomic signatures were detected with accuracy. Lastly, several fecal PDAC marker species were detectable in pancreatic tumor and non-tumor tissue.

Recommended by our community

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

We have found that in mice whose intestines are colonized with bacteria from preterm infant stool, interferon and antibody responses to RSV infection are diminished, and neutrophil trafficking to the lung is enhanced, which could worsen tissue damage.

What are the consequences for the patient?

Our data suggest that the microbiome contributes to the heightened risks of severe RSV in preterm infants, by dysregulating the immune response. We are currently working to identify specific bacteria or metabolites that are responsible for these effects, which could potentially offer therapeutic strategies to improve immune function in preterm infants by manipulating the microbiome.

BMI 22.29

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

Creating a microphysiological model to study the interactions between digestive epithelial cells and anaerobic microbiota from patients samples.

What are the consequences for the patient?

Today, the model allows researchers to better understand the physiopathology of gut inflammation and to reproduce ex vivo the specific interactions between eucaryote cells and bacteria. Ultimately, this model will allow clinicians to tailor the specific treatment of inflammatory bowel diseases.

BMI 22.27

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

Studying gastric microbiota in patients with gastric malt lymphoma, which has never been done before.

What are the consequences for the patient?

Routinely offer antibiotics to patients with gastric malignant lymphoma, even if they do not have Helicobacter pylori infection.

BMI 22.25

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

We have been able to, for example, extend our screening to include SARS-CoV-2 without which it would have been impossible to continue working under extremely difficult circumstances during a global pandemic. Safety is the utmost issue in our methodology and the national grant has kept us on the highest level of safety.

What are the consequences for the patient?

We have been able to minimize risks of the transplant process, demonstrated by the lack of adverse events.

BMI 22.28