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The Human Microbiome in Focus: Probiotics, Modulation and Translation – Part 2

Microbiome conference in Amsterdam

The 4th Microbiome R&D and Business Collaboration Forum: Europe explored microbiota both inside and outside the gut and examined the role of the human microbiome in various diseases with a focus on modulation and biotherapeutic translation.

Last week, we published Duc H. Le’s summary of some of the presentations on day one. Here’s the second day summed up.

Developing an Artificial Bacterial Consortium to Modulate Microbiota of Frail Elderly

The microbial composition of the gut changes gradually with ageing and is influenced by habitual diet and health status. In one cohort studied, frail elderly had a microbiota profile characterised by an increase in Bacteroidetes and a low microbiota diversity compared to healthy elderly. Paul W. O’Toole and colleagues (Cork, Ireland) developed a bacterial artificial consortium that mimics the healthy gut microbiota composition and potentially rectifies the gut microbiota of the frail elderly.

More than 700 strains belonging to 90 bacterial species and one archaeon species were isolated in ore culture from the faecal samples of 7 healthy donors. 100 different commensal strains were finally selected from the initial collection, reflecting species with a range of abundance values in the gut microbiota based on the existing literature, and having considered the genetic similarity of the strains in order to maximise the genetic diversity of the consortium.

To further investigate the safety of the 100 selected strains, the researchers determined their MIC values using a panel of 7 antibiotics. This rationally selected consortium of 100 commensal gut microbial strains could be used as a live biotherapeutic consortium for the modulation of the elderly gut microbiota.

Circulating Bile Acids as Biomarkers of Metabolic Health

The gut microbiota modulates bile acids (BA) enterohepatic circulation, and the profile of these potent cell signalling molecules in the blood. However, human data confirming dietary modulation of circulating BA profiles and subsequent regulation of physiological homeostasis remains elusive.

The EU (ERA-HDHL) funded project CABALA_DIET&HEALTH, led by Fondazione Edmund Mach, Italy with partners in the UK (University of Reading), Italy (University of Insubria), Ireland (University College Cork) and Israel (Ben Gurion University of the Negev), aims to establish circulating BA profiles as biomarkers of health. Using samples from existing studies the researchers will correlate circulating BA profiles with adherence to the Mediterranean diet and measures of metabolic health (BMI, insulin/glucose and lipid homeostasis).

In a short-term randomised controlled trial (RCT), they will measure the ability of probiotics, prebiotics and polyphenols to modulate post-prandial BA profiles. In a long-term (18-month), large-scale (n=300) existing dietary and lifestyle RCT, they will also measure how polyphenol-rich foods and exercise, through BA signalling, promote metabolic health in susceptible individuals.

Finally, the researchers will link BA profiles with microbiome signatures using high-resolution metagenomics and establish the molecular basis of BA regulation of immune and metabolic homeostasis by measuring the relative BA-metabotype receptor activation potential.

Genetically Modified Probiotics as Biotherapeutics

There is a strong interest in unravelling the molecular mechanisms involved in industrial robustness, cognate stress resistance and health-promoting phenotypes of food bacteria. This strategy, which involves the construction of genetically modified probiotics, can be divided into three distinct approaches: (i) delivery: engineering technological robustness; (ii) survival: improved competitiveness in the gut and other mucosa, and (iii) efficacy: improved therapeutic properties.

During the past two decades, major health benefits of genetically modified probiotics have been demonstrated using animal models. The field has recently moved into the era of human clinical trials which showed biological containment, safety, and tolerability with preliminary data demonstrating positive efficacy in human subjects against oral mucositis. The potential of genetically modified probiotics as therapeutic tools for their safe and efficient use in human health was outlined.

Catherine Daniel and colleagues (Lille, France) showed that a recombinant lactic acid bacterium producing a Yersinia protein has a dual potential in mice models: inhibition of experimental intestinal inflammation and protection against a pathogenic Yersinia challenge. Moreover, they developed multicoloured bioluminescent bacteria for simultaneous visualisation of different lactic acid bacterial strains by in vivo imaging in live mice.

The global series of microbiome meetings continues November 2 – 3 in San Diego. View the agenda.

5th Microbiome R&D and Business Collaboration Forum: USA

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