From Superbugs to Diversity: The Two Roads of Microbiome Science

For more than a century, scientists have been fascinated by the microbes in our gut. In the early 1900s, Nobel laureate Elie Metchnikoff suggested that sour milk and yogurt could slow aging. He believed lactic acid bacteria suppressed “putrefactive microbes” that produced toxins in the colon. His idea birthed the first generation of “hero microbes” — lactic acid tablets sold as cures for diarrhea, skin conditions, and even liver disease.

A new review in The Journal of Nutrition — From the Laboratory to the Plate: How Gut Microbiome Science Is Reshaping Our Diet — traces this story and highlights two very different research directions that emerged from those early days.

Path One: The Superbug Quest

This path seeks individual strains with miraculous health benefits. Over the decades, strains like Lactobacillus casei Shirota (Yakult), Lactobacillus rhamnosus GG, and most recently Akkermansia muciniphila have been developed and tested.

These “superbugs” are often studied for very specific molecular actions:

• Lactic acid production, which lowers gut pH and inhibits pathogens.

• Mucin degradation (e.g., by A. muciniphila), which strengthens the gut barrier and improves metabolic signaling.

• Immune modulation, such as influencing dendritic cells and regulatory T-cells through bacterial surface proteins.

• Metabolite production, including vitamins, antimicrobial peptides, or signaling lipids.

It’s a reductionist, pharmaceutical-style approach: one microbe, one molecule, one effect. This makes for compelling products and headlines — but risks oversimplifying a highly complex ecosystem.

Path Two: The Diversity Perspective

The second path doesn’t look for a single magic bullet. Instead, it investigates how microbial diversity and nutrient networks sustain health by interacting with our immune system and metabolism.

Here, the focus is on metabolites and signaling cascades that emerge only when diverse microbes cooperate:

• Short-chain fatty acids (SCFAs) like acetate, propionate, and butyrate, produced when microbes ferment dietary fibers. These molecules regulate gene expression via histone deacetylase (HDAC) inhibition, fuel colonocytes, and promote anti-inflammatory T-regulatory cell development.

• Polyphenol metabolism, where gut microbes convert plant polyphenols into bioactive compounds with antioxidant and anti-inflammatory effects. The presence or absence of specific converters explains why some people benefit more than others.

• Toxic signaling: microbial byproducts like hydrogen sulfide (H₂S), lipopolysaccharides (LPS), or trimethylamine (TMA, converted to TMAO in the liver) can trigger inflammation, endothelial damage, or metabolic stress when the system loses balance.

• Immune crosstalk: Microbial metabolites interact with host pattern recognition receptors (PRRs) such as Toll-like receptors, shaping mucosal immunity and the balance between tolerance and inflammation.

This path emphasizes ecosystem resilience: health comes from a balanced, adaptable network of microbes, nutrients, and immune signals — not a single strain.

Why Diversity Matters More

Evidence increasingly supports the diversity path. People who consume >30 types of plant foods per week harbor richer microbial ecosystems than those who eat fewer than 10. Germ-free animal studies show that without SCFAs, the immune system remains underdeveloped and pro-inflammatory. And importantly, loss of diversity across generations (as seen in low-fiber Western diets) can be irreversible — reinoculation, not diet alone, is sometimes needed to restore species.

Yet, despite this evidence, diversity research remains less glamorous. It doesn’t fit neatly into a capsule. It can’t be marketed as “one strain to fix it all.” And so the commercial spotlight shines on the superbug path, even though the long-term, systems-level evidence points to the broader, less sexy ecosystem approach.

The Future: Integration

Both paths have value. Probiotic discoveries gave us yogurt, functional dairy, and clinically proven strains for certain conditions. But the diversity-driven science — exploring how fiber, polyphenols, microbial networks, and host immunity interact — may hold the real key to resilience, chronic disease prevention, and healthy aging.

If the microbiome is a forest, the superbug approach searches for the tallest tree; the diversity approach protects the entire ecosystem. And when it comes to sustaining health over a lifetime, it may be the forest, not the tree, that matters most.

✨ In short:

The future of gut health isn’t about finding a miracle microbe — it’s about nurturing the ecological orchestra inside us.

Hiol, A., & Veiga, P. (2025). From the laboratory to the plate: How gut microbiome science is reshaping our diet. The Journal of Nutrition. Advance online publication. https://doi.org/10.1016/j.tjnut.2025.08.032

#Gut microbiome, #Probiotics and prebiotics, #Microbial diversity, #Immune modulation, #Precision nutrition