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

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

The existing opinion that the microbiota is another organ in the human body that requires special attention has been confirmed.
The study of the intestinal microbiota is a complex process that requires not only standardization for an objective assessment of the results of the study, but also the development of research methods, including genetic ones, that make it possible to isolate and differentiate not only strains of microorganisms, but also their metabolic products. One of the most difficult issues is microbiota transplantation for the purpose of targeted therapy of diseases.

What are the consequences for the patient?

The study of the intestinal microbiota and its metabolic products in the future will allow the targeted use of methods for its correction in order to optimize the treatment of various diseases.

BMI 22.21

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

The national grant made it possible to study in detail the effect of antibiotic therapy on the qualitative and quantitative changes in the composition of the intestinal microbiota, as well as on the concentration and spectrum of bacterial metabolites - short-chain fatty acids. The effect of antibiotic therapy on selective intestinal permeability was studied for the first time. A relationship has been established between antibiotic therapy and the occurrence of symptoms characteristic of functional diseases of the gastrointestinal tract.

What are the consequences for the patient?

It is expected that the results of the project will make it possible to determine an additional pathogenetic mechanism for the formation of symptoms of functional gastrointestinal diseases and become the basis for developing the optimal way to prevent it

BMI 22.20

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

Spondyloarthritis (SpA) and Rheumatoid arthritis (RA) are among the most common chronic inflammatory rheumatic diseases and these diseases progression can lead to irreversible joint and bone damage. SpA and RA are major causes of functional disability, with severe impact in daily activities, in mental health and in patient’s quality of life. The introduction of biological disease-modifying antirheumatic drugs (bDMARDs), such as TNF inhibitors (TNFi) has started a new era in the treatment of SpA and RA, with remarkably efficacy. Neverthless, a significant percentage of patients develop severe adverse events or are still non responders or incomplete responders to these expensive treatments. Biocodex Microbiota Foundation grant allow us to characterize microbiota in patient starting bDMARDs and after 14 weeks. This represents the possibility to identify biomarkers at baseline contributing to the identification of patients with more potential to respond to TNFi therapy.

What are the consequences for the patient?

The identification of microbiota profiles before treatment that can be related to therapeutic efficacy of bDMARDs are crucial to guide therapeutic decision. Patients will benefit of a more precise treatment. In a near future we expect to promote corrective actions to directed microbiota and with these actions to improve bDMARDs therapeutic efficacy.

BMI 22.19