The Other Key to Unlocking the French Paradox

4 years ago, back when I worked at Probiotical in Italy, I read the 1st book on the microbiome of what would become a long series. It was The Diet Myth, by Tim Spector, and looked at a number of false ideas on diet, now being challenged thanks to the better understanding of the role of the gut microbiome in our physiology, metabolism and health. One of the most original ideas exposed by Tim Spector was about the French Paradox.

What is the French Paradox ?

French people cultivate an unapologetic love for cheese, bread (baguette), butter, cream, chocolate, red meat and red wine. Although on average the French have a high-fat diet, they (we) stay relatively protected from obesity and cardiovascular disease, with less than half the levels found in the USA. A mystery that has been puzzling nutritionists worldwide for decades.

The scientific story served to explain this phenomenon when I was a student in nutrition at the Paris Institute for Life Sciences (AgroParisTech) was that the relatively high consumption of red wine exerted these protective effects.

Red wine is rich in polyphenols, compounds which we now know are beneficial for a resilient, diverse microbiota (1–3).

However, this explanation is probably partial.

The Other Key to Unlocking the French Paradox

Spector’s intuition about the French Paradox came from his study of French cheeses consumption, and his understanding of the microbiome, which he describes as an ecosystem that can be compared to a forest. If the ecosystem is a thriving rainforest, a mix of intertwined species interacting with each other, it appears as a healthy, diverse and resilient picture. On the other hand, a microbiome with few species or dominated by just one or two predominant bacteria look more like a desert, and is recognized as a less positive baseline for health, as important functions could be missing altogether, and if a species is lost, there is no redundancy played by other species, simply because there are no other species to jump in.

Now about French cheese. Every locality in France has its own cheese specialty. A key feature of traditional French cheese is that it ought to be produced from raw milk — to preserve all the goodness of the bacteria naturally present in the milk. And in the past, each locality, if not each farm, had its own production secrets — some, as related by Spector, not as appetizing as I would wish to describe, such as the starter preparation sitting on a bowl in a barn, a liquid stink that was comprised of the specific mix of bacteria left to self-replicate, with a little add-on of milk or even horse urine to the blend every now and then to ensure the culture thrives and has its own unique set of flavor. A cloth could then be dipped in the bacterial soup and brushed on the surface of the cheese to ensure it develops its proper, characteristic tones during maturation.

Will you even enjoy French cheese the same way?

Although hygiene measures have become stricter since that time, what Spector caught right is the likely important contribution of the diversity of raw milk French cheeses to the nation’s microbiota diversity — not only each cheese brings its own set of microbes, but it is not uncommon to taste several types of cheeses in a same meal.

The Data is Catching Up on the Intuition

The story of the French biotech TargEDys, the company where I now work, is the story of bringing to light one of the possibly many mechanisms of action confirming how well-founded was Tim Spector’s intuition. Prof. Serguei Fetissov, researcher in neuroendocrinology, worked for most of his life on indicators from the microbiome associated to eating disorders. In the beginning, he tried to use such signals as a diagnosis tool for anorexia and bulimia. Until he realized one of these signals he had identified, namely Caseinolytic Peptidase B (ClpB for short) was inversely correlated with Body Mass Index (4) and he thought there could be a causality link behind this association.

ClpB negative association with body weight in humans, from Arnoriaga-Rodríguez, 2020, Microbiome (ref. 4).

Indeed, he discovered, with Prof. Pierre Dechelotte, that the ClpB molecular structure has a sequence of amino acids in common with the hormone alpha-MSH, one of the main satiety hormones. By “looking alike” the satiety hormone, the protein is recognized in the gut as the enhancer of the feeling of fullness, and triggers a pathway that tunes down hunger. For me, the effect was I simply didn’t want to reach for these Nutella cookies anymore.

ClpB and its pharmacophore, the red sequence, active like alpha-MSH, illustration from Manon Dominique

What Does All This Have To Do With Cheese?

The bacterium TargEDys identified and isolated to formulate a supplement favoring satiety and weight loss is a microorganism called Hafnia alvei that was traditionally found (and still is) in cheese, in particular camembert cheese (5), but not only. It was also found in Gouda (6), French Livarot (7), goat’s milk cheese from Sierra de Aracena (8), etc. So, it could be the case that the regular consumption of such cheeses, while participating to fat intake, also engages in a healthy, diverse microbiome that supports a normal feeling of fullness and a happy relationship with food.

Cheers to you, your microbes, your wine polyphenols and your favorite cheese!


1. Nash V, Ranadheera CS, Georgousopoulou EN, Mellor DD, Panagiotakos DB, McKune AJ, Kellett J, Naumovski N. The effects of grape and red wine polyphenols on gut microbiota — A systematic review. Food Res Int. 2018 Nov;113:277–287.

2. Moreno-Indias I, Sánchez-Alcoholado L, Pérez-Martínez P, Andrés-Lacueva C, Cardona F, Tinahones F, Queipo-Ortuño MI. Red wine polyphenols modulate fecal microbiota and reduce markers of the metabolic syndrome in obese patients. Food Funct. 2016 Apr;7(4):1775–87.

3. Le Roy CI, Wells PM, Si J, Raes J, Bell JT, Spector TD. Red Wine Consumption Associated With Increased Gut Microbiota α-Diversity in 3 Independent Cohorts. Gastroenterology. 2020 Jan;158(1):270–272.e2.

4. Arnoriaga-Rodríguez M, Mayneris-Perxachs J, Burokas A, Pérez-Brocal V, Moya A, Portero-Otin M, Ricart W, Maldonado R, Fernández-Real JM. Gut bacterial ClpB-like gene function is associated with decreased body weight and a characteristic microbiota profile. Microbiome. 2020 Apr 30;8(1):59.

5. Mourgues R, Vassal L, Auclair J, Mocquot G, Vandeweghe J, 1977. Origine et développement des bactéries coliformes dans les fromages à pâte molle. INRA Ed., vol. 57, no. 563–564, pp. 131–149.

6. Joosten HM and Northolt MD, 1989. Detection, growth, and amine-producing capacity of lactobacilli in cheese. Appl Environ Microbiol. 55, 2356–9.

7. Mounier J, Monnet C, Jacques N, Antoinette A and Irlinger F, 2009. Assessment of the microbial diversity at the surface of livarot cheese using culture-dependent and independent approaches. Int J Food Microbiol. 133, 31–7.

8. Martin-Platero AM, Maqueda M, Valdivia E, Purswani J and Martinez-Bueno M, 2009. Polyphasic study of microbial communities of two spanish farmhouse goats’ milk cheeses from sierra de aracena. Food Microbiol. 26, 294–304.



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Nina Vinot

Nina Vinot

My Education is in Biology, Agronomy and Nutrition My Career is in Health-Promoting Bacteria My Passion is to Benefit Life, Happiness and the Planet