Unlocking the full potential of probiotics: refocusing on microbial demands

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Unlocking the full potential of probiotics: refocusing on microbial demands

The human gut microbiome—trillions of bacteria, fungi, and other microbes living in our digestive tract—has been called our “forgotten organ” for its vital role in digestion, immunity, and even mental health. Over the past decade, scientists have uncovered how changes in this microbial community link to diseases like inflammatory bowel disease (IBD), diabetes, and antibiotic-associated diarrhea. This has sparked interest in bacteriotherapy—using live microbes or their products to treat illness—including fecal microbiota transplantation (FMT) and probiotics.

But while probiotics (defined by the FAO/WHO as “live microorganisms which when administered in adequate amounts confer a health benefit on the host”) are widely used, their effectiveness is often inconsistent. Why? According to Marie Joossens, a microbiologist at Ghent University’s Laboratory of Microbiology, we’ve been missing a critical piece: the microbial perspective. To unlock probiotics’ full potential, we need to focus on what the probiotic strain itself needs to thrive in a person’s unique gut ecosystem.

Probiotics aren’t one-size-fits-all—strain specificity matters

You’ve probably seen probiotic labels promising “10 billion CFUs” or “contains Lactobacillus.” But here’s the secret: not all strains of the same bacteria work the same way. Most health benefits of probiotics are strain-specific—meaning two strains of Bifidobacterium longum can have wildly different effects on your gut.

For example:

  • A 2015 study found that one strain of Bifidobacterium longum protected mice from acute colitis, while another did not.
  • Two strains of Akkermansia muciniphila (a mucus-eating bacterium linked to gut health) showed similar anti-inflammatory effects in lab dishes—but only one worked for mice with chronic colitis.
  • Lactobacillus murinus strains vary in their ability to reduce inflammation in human gut cell models.

This strain specificity explains why promising lab results often fail in people. Lab conditions are controlled—they help bacteria grow easily—but the human gut is a complex, dynamic ecosystem where microbes compete for food, space, and resources. A probiotic that thrives in a petri dish might struggle to survive in your gut, where “good” and “bad” microbes are already locked in a balance.

Your gut’s “resistance” to probiotics

Even if a probiotic strain is effective in labs, your body’s own microbiome and immune system can reject it. Studies in mice show that the native gut bacteria “resist” colonization by probiotics—meaning the probiotic can’t stick around long enough to work. In humans, how well a probiotic colonizes the gut varies person to person: some people’s guts are “receptive” to a strain, while others’ are not.

Why? Two key factors:

  1. Your microbiome: If your gut already has microbes that occupy the same niche (food, space) as the probiotic, the probiotic can’t compete.
  2. Your immune system: Local immune responses in the gut can target and clear probiotics before they take hold.

This is why “generic” probiotics—like the ones you buy at the grocery store—might work for some people but not others. Your gut is unique, and so is its response to probiotics.

Host factors: Genetics and diet shape probiotic success

Your genes and what you eat also play big roles. For example:

  • Genetics: A 2018 study found that healthy people with genetic risk variants for IBD have less Roseburia—a bacterium that makes butyrate, a compound that calms gut inflammation. If you’re an ulcerative colitis patient with these variants, a Roseburia probiotic might not work because your gut is already “programmed” to have less of it.
  • Diet: Probiotics need food to grow. If your diet lacks the fibers or nutrients a strain needs, it can’t thrive. But changing diet is hard—so for now, we have to work with what people already eat.

These factors are “unchangeable” for most people. That’s why the future of probiotics isn’t about “better” strains—it’s about matching strains to people.

Antibiotics, probiotics, and the risk of “harming” your gut

One of the most well-supported uses of probiotics is preventing antibiotic-associated diarrhea (AAD). Antibiotics kill “good” gut bacteria along with bad ones, disrupting the microbiome and letting pathogens like C. diff take over. Probiotics can fill the gap, competing with pathogens for space.

But here’s a catch: research shows that probiotics can slow down your gut’s recovery after antibiotics. A 2018 Cell study found that probiotics “blocked” the return of native gut bacteria in people who took antibiotics. Why? The probiotics were competing with the native microbes trying to regrow.

The solution? Autologous FMT—using your own stool (collected before antibiotics) to repopulate your gut. It works because your native microbes are already adapted to your gut. But it’s not practical for everyone—especially if you took antibiotics for a gut infection.

The future: Personalized probiotics for targeted health

So, what’s the fix for probiotics’ inconsistent effectiveness? Joossens argues for a microbe-first, person-first approach:

  1. Match the strain to the need: If you have ulcerative colitis, use a strain that makes butyrate (like Roseburia)—but only if your gut is “receptive” to it.
  2. Pre-screen patients: Test a person’s microbiome and genetics to see if a strain will work for them.
  3. Optimize the environment: Help the probiotic thrive by providing the right nutrients (if possible).

This isn’t “one-size-fits-all”—it’s personalized medicine for your gut. And it’s already starting: tools like the Simulator of the Human Intestinal Microbial Ecosystem (SHIME) let scientists test probiotics in a lab model of your gut (using your stool sample). But we need more research to make this mainstream.

Conclusion

Probiotics have huge potential—but we’re not using them right. The key is to stop treating all probiotics as the same and start focusing on what each strain needs to survive in your gut. By combining microbiology, genetics, and personalized medicine, we can turn probiotics from a “maybe” into an evidence-based therapy for diseases like IBD, AAD, and more.

Marie Joossens is supported by a fellowship from the Research Foundation – Flanders (FWO). She declares no conflicts of interest.

References

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