Introduction
Claims about “improving the gut microbiome” are widespread, but what would improvement actually mean? How do we establish which microbial changes contribute to disease, and which simply reflect it?
Research on bacterial metabolism of medications raises questions about how the microbiome might influence treatment efficacy and toxicity. What would it take to translate these findings into reliable tests and effective therapies?
In this episode, gastroenterologist and researcher Prof. Harry Sokol examines these questions, discusses the development of Faecalibacterium prausnitzii as an investigational treatment, and considers what current evidence can tell us about dietary advice and commercial microbiome testing.
[02:50] Harry Sokol’s work
[04:36] Defining healthy microbiome
[06:48] Do we have causal evidence?
[11:05] FMT evidence
[15:29] Diet-microbiome claims
[20:45] Emulsifiers & IBD research
[22:54] Microbiome-drug interactions
[30:23] Bacteria as a drug?
[38:09] Microbiome testing
[44:36] Key ideas segment (Premium-only)
Episode Resources
- Join the Sigma newsletter for free
- Subscribe to Sigma Nutrition Premium
- Enroll in the next cohort of our Applied Nutrition Literacy course
- Exeliom Biosciences
- Book: MICROBIOME: Science, Promises and Lies
- Instagram: @harry_sokol
- LinkedIn: Prof. Harry Sokol
- Related episodes:
Guest Information
Prof. Harry Sokol is a Professor in the Gastroenterology department of Saint-Antoine Hospital (Sorbonne Université, Paris) and is is an internationally recognized expert in the inflammatory bowel disease (IBD) and gut microbiota fields.
His work on the role of gut microbiota in IBD pathogenesis led to landmark papers, including identifying the pivotal role of the commensal bacteria Faecalibacterium prausnitzii in gut homeostasis and IBD. Currently, his work focuses on deciphering gut microbiota–host interactions in health and disease to better understand their role in pathogenesis and develop innovative treatments.
Prof. Sokol currently is the president of the French group of Fecal Microbiota Transplantation and is Associate Editor for Gastroenterology. He co-founded Exeliom biosciences.
Study Notes
The gut microbiome can influence disease processes and treatment responses. However, detecting a microbial difference, changing that difference, and improving a patient’s health are separate scientific questions. Prof. Harry Sokol explains how to evaluate these links, why some microbiome interventions succeed while others disappoint, and what is required to turn promising biology into useful medicine.
Useful Terminology
- Microbiota: The microorganisms living in a particular environment, such as the gastrointestinal tract.
- Microbiome: A term often used broadly for the microbial community, its genetic material, and its surrounding ecological context. In the episode, discussion focuses mainly on gut bacteria and their functions.
- Taxonomic composition: Which organisms are present and their relative abundances. This describes community membership rather than directly measuring what the community does.
- Functional characterisation: Examining microbial capabilities or activities, such as metabolising a drug or producing a biologically active compound. Genetic potential and actual activity are related but different measurements.
- Microbial diversity: A description of community variety. Different indices capture different combinations of richness and evenness; diversity is not a direct measurement of health.
- Dysbiosis: An altered microbial community described in relation to a reference state. Without a validated reference and clinical context, the label does not establish a diagnosis or a treatment target.
- Reverse causality: Disease changes the microbiome, rather than the observed microbial change causing disease.
- Faecal microbiota transplantation (FMT): Administration of a preparation derived from screened donor stool to alter the recipient’s intestinal microbial ecosystem.
- Engraftment: Establishment or persistence of donor-derived microorganisms in a recipient. Its definition and measurement depend on the study.
- Live biotherapeutic product (LBP): A product containing live organisms developed for a therapeutic purpose. Sokol’s example is the investigational Faecalibacterium prausnitzii strain EXL01.
- Pharmacokinetics: How a drug is absorbed, distributed, metabolised and eliminated. Microbial metabolism can alter the drug exposure experienced by the host.
- Clinical utility: Whether using a test improves decisions or outcomes compared with care without the test. Finding an association or producing a detailed report does not establish utility.
1. What Would a Healthy Microbiome Actually Mean?
There is no single validated normal composition
- Sokol’s starting point: We cannot currently define precisely what a normal gut microbiome is. Important microbial functions remain incompletely understood.
- Comparing healthy and diseased groups can identify patterns, but a group average is not automatically a reference range for an individual.
- A bacterial abundance may have different significance depending on the organism’s strain, its activity, the surrounding community and the host’s clinical context.
- Describing a community as more diverse, or closer to a selected healthy reference group, does not by itself establish that a person is healthier.
From naming organisms to understanding their function
- Sokol argues that the field needs to move beyond asking which bacteria are present and towards asking what they are doing.
- Functional redundancy: Different organisms can perform similar tasks. A taxonomic