Diet outperforms microbial transplant to drive microbiome recovery in mice (April 2025) Diet

NiroZ · May 1, 2025

https://www.nature.com/articles/s41586-025-08937-9
https://scienmag.com/diet-beats-microbial-transplants-in-microbiome-recovery/

A new and compelling study published in Nature in 2025 by Kennedy et al. elucidates the intricate interplay between a Western-style diet and microbiome recovery dynamics following antibiotic perturbation in mice. ... This investigation specifically contrasts microbiome recuperation trajectories between mice consuming either a traditional regular chow (RC) diet or the WD, revealing profound divergence in both speed and functional restoration of the microbiota.

Fundamentally, the research highlights that mice maintained on regular chow experience a rapid and orderly succession of microbial populations after antibiotic exposure, effectively restoring both taxonomic balance and metabolic capacity. This successional recovery is underpinned by syntrophic cross-feeding interactions, where microbial taxa cooperate by exchanging metabolic byproducts, fostering a resilient and functionally diverse ecosystem. In stark contrast, mice fed the WD exhibit a stalled recovery dominated by a single taxon that monopolizes available nutrient resources and fails to support the emergence of syntrophic networks, resulting in prolonged dysbiosis.

Findings suggest that the RC diet fosters a nutrient landscape conducive to cooperative metabolic exchanges—these cross-feeding relationships enhance microbial diversity and functional redundancy, buffering the community against perturbations. Conversely, the WD appears to create a nutrient milieu that favors opportunistic expansion of select microbes capable of rapidly exploiting energy-dense substrates, yet these dominant strains do not release metabolic byproducts that could sustain syntrophic partners, effectively undermining community resilience.

Abstract
A high-fat, low-fibre Western-style diet (WD) induces microbiome dysbiosis characterized by reduced taxonomic diversity and metabolic breadth1,2, which in turn increases risk for a wide array of metabolic3,4,5, immune6 and systemic pathologies. Recent work has established that WD can impair microbiome resilience to acute perturbations such as antibiotic treatment7,8, although little is known about the mechanism of impairment and the specific consequences for the host of prolonged post-antibiotic dysbiosis. Here we characterize the trajectory by which the gut microbiome recovers its taxonomic and functional profile after antibiotic treatment in mice on regular chow (RC) or WD, and find that only mice on RC undergo a rapid successional process of recovery. Metabolic modelling indicates that a RC diet promotes the development of syntrophic cross-feeding interactions, whereas in mice on WD, a dominant taxon monopolizes readily available resources without releasing syntrophic byproducts. Intervention experiments reveal that an appropriate dietary resource environment is both necessary and sufficient for rapid and robust microbiome recovery, whereas microbial transplant is neither. Furthermore, prolonged post-antibiotic dysbiosis in mice on WD renders them susceptible to infection by the intestinal pathogen Salmonella enterica serovar Typhimurium. Our data challenge widespread enthusiasm for faecal microbiota transplant (FMT) as a strategy to address dysbiosis, and demonstrate that specific dietary interventions are, at a minimum, an essential prerequisite for effective FMT, and may afford a safer, more natural and less invasive alternative.

I haven't been able to read the study itself, so how it compared diet to FMT is unclear so I'm not sure how well it establishes it's claim (it may have just been modelling). But it provides solid evidence, given the our relationship to the microbiome seems similar to that of mice, that diet can effect antibiotic recovery.

Michael Harrop · May 2, 2025

Some very bold claims locked behind a paywall. There is a large body of evidence contradicting their claims (https://humanmicrobiome.info/antibiotics/).

Until this is made open-access, it should be ignored by the general public.

One example is that mice naturally eat each other's poop, so we'd have to see what steps they took to prevent that in the "diet only" group.

NiroZ · May 2, 2025

It's quite plausible that they kept the mice in individual cages, which is common practice.

Going off your link, this study suggests sharing poop can have the opposite effect in mice. This study supports the idea that you need some kind of supplementation to address dysbiosis and that FMT doesn't work in mice.

Of the studies listed that suggest FMT is effective in regards to recovering from antibiotics, they specifically discuss it in regards to countering anti-microbial resistance, which is not the same as restoring the microbiome to how it was before.

None of your studies mention diet, so honestly I'm not sure what this large body of contradictory evidence is. So I think the general public should take away from this that eating a healthier diet after antibiotics can counter the effects. It's what they should be doing anyway, what exactly is the harm?

Michael Harrop · Saturday at 4:19 PM

NiroZ said:
None of your studies mention diet, so honestly I'm not sure what this large body of contradictory evidence is.

The large body of evidence indicates that antibiotics do permanent damage. They kill off the host-native microbes that have been evolving alongside us for millions of years and get passed down generationally.

Presumably, they are feeding the mice regular chow in most experiments that don't mention diet.

How does it make sense that simply eating healthy is going to restore the microbes that were killed off, when actually transplanting the microbes back does not?

We also have a plethora of evidence in humans that eating healthy is insufficient to reverse disease states, and one must resort to FMT. This is why most of us are doing FMT. We've already tried every healthy diet.

More evidence:

NiroZ said:
It's what they should be doing anyway, what exactly is the harm?

It's misleading that the damage from antibiotics can simply be reversed with a healthy diet. That's a dangerous notion to spread.

NiroZ · Saturday at 7:12 PM

Michael Harrop said:
The large body of evidence indicates that antibiotics do permanent damage.

That's too broad a statement, even Missing Microbes acknowledges different antibiotics have different effects. I'm sure some, or some combinations can, that's how they get rid of H. Pylori after all. However, They have to go really hard to get rid of H. Pylori, I wouldn't be surprised if other microbes are similar.

Presumably, they are feeding the mice regular chow in most experiments that don't mention diet.

But they haven't tried comparing different diets.

How does it make sense that simply eating healthy is going to restore the microbes that were killed off, when actually transplanting the microbes back does not?

Now you're moving the goalposts. This study just hinting at the potential for healthy people to recover from antibiotics with diet. Obviously, for people with complex health issues it's different.

We also have a plethora of evidence in humans that eating healthy is insufficient to reverse disease states

Citation needed. There have been miracle cures reported by FMT, but the vast majority don't report that. I mean, are you cured? Similarly, there have been miracle cures reported from people via diet, but again, the vast majority don't report that. But again, you're arguing beyond what the study claims. And from a theoretical standpoint, to change an ecosystem, both introducing new species and changing the nutrients available are valid avenues.

More evidence:

https://humanmicrobiome.info/diet/#impacts-limitations

https://humanmicrobiome.info/diet/#variation-from-person-to-person

I'm not going on another treasure hunt, given last time, copy paste the relevant sections if you think they apply.

It's misleading that the damage from antibiotics can simply be reversed with a healthy diet. That's a dangerous notion to spread.

You're operating off a misunderstanding. The claim is that a unspecified healthy diet may correct the negative impact of antibiotics, for non-complex situations. Obviously, all the advice about finding a diet that's healthy for you applies. And I'm not aware of any negative impact from doing that.

Edit: And encouraging people to go on a healthy diet is better than what they usually do which is to take probotics. I've heard little efficacy of probotics, but there was that one study that found them harmful. evidence of efficacy

indigo34 · Sunday at 11:27 AM

NiroZ said:
Of the studies listed that suggest FMT is effective in regards to recovering from antibiotics, they specifically discuss it in regards to countering anti-microbial resistance, which is not the same as restoring the microbiome to how it was before.

I suppose you haven't read this:

Post-Antibiotic Gut Mucosal Microbiome Reconstitution Is Impaired by Probiotics and Improved by Autologous FMT (2018)
https://www.cell.com/cell/fulltext/S0092-8674(18)31108-5?

Michael Harrop · Sunday at 11:44 AM

NiroZ said:
But they haven't tried comparing different diets.

That's irrelevant. Their central claim is that simply feeding mice "regular chow" reconstitutes their microbiome after antibiotics.

NiroZ said:
Now you're moving the goalposts. This study just hinting at the potential for healthy people to recover from antibiotics with diet. Obviously, for people with complex health issues it's different.

I don't agree. And it's not a "hint", it's an extremely bold claim. You're playing down their claims & conclusions, but other people will not.

I think further argumentation is not useful until we can actually read the study.

NiroZ said:
Citation needed.

A very easy example is all of us who are trying FMT. We've already tried a variety of healthy diets and FMT is the only thing that has brought relief. There's further citations in the Diet links I shared. There's also more here:

The summary/conclusion of these links (and the Diet ones) is that you must restore/add the necessary microbes in order to be able to tolerate a wide range of "healthy" foods, and without those microbes, those "healthy" foods can be harmful.

NiroZ said:
I mean, are you cured?

I have indeed cured various conditions and then made them worse again with a new donor.

NiroZ said:
And from a theoretical standpoint, to change an ecosystem, both introducing new species and changing the nutrients available are valid avenues

Read the Diet links I shared. Diet is far more limited.

NiroZ said:
I'm not going on another treasure hunt, given last time, copy paste the relevant sections if you think they apply.

I linked directly to the relevant sections. It's not a "treasure hunt" it's the "plethora of evidence" you asked me to cite.

NiroZ said:
I've heard little efficacy of probotics, but there was that one study that found them harmful.

Review the probiotic guide.

NiroZ · Sunday at 9:31 PM

Michael Harrop said:
That's irrelevant. Their central claim is that simply feeding mice "regular chow" reconstitutes their microbiome after antibiotics.

I think a more precise summary is that for the antibiotic regime that they were on, they recovered on regular chow, but not a western diet, showing that eating a western diet can have an impact.

I don't agree. And it's not a "hint", it's an extremely bold claim. You're playing down their claims & conclusions, but other people will not.

Can you please be more explicit over what your concern is, because I feel like you're shooting the messenger here for something they're not even saying. What exactly do you think I'm trying to achieve by posting this study?

Michael Harrop said:
The summary/conclusion of these links (and the Diet ones) is that you must restore/add the necessary microbes in order to be able to tolerate a wide range of "healthy" foods, and without those microbes, those "healthy" foods can be harmful.

Those links don't say that. And that's not a point I'm arguing against, please focus on what I'm actually claiming.

Michael Harrop said:
Diet is far more limited.

Maybe the best way to phrase my request would to to ask of if you know of any studies, most likely meta-studies of longitudinal studies that found no additional species over time, that show that regardless of intervention, that a adult microbiome does not allow new species into the microbiome without FMT. And show that even though bacteria copy genes from each other all the time not to mention they evolve, they cannot adapt sufficently.

Michael Harrop said:
Review the probiotic guide.

I can't help but feel that your guide proves my point. Very few people do sufficient research, and in many cases there isn't sufficient research anyway, so they just go to the supermarket and grab a bottle. I'd also suggest you add this study to the guide which shows the control group's microbiome recovering to normal but not the probiotic group.

How do you feel about my point that eating a diet that is healthy for you is harmless thing to try in order to recover from antibiotics?

Michael Harrop · Monday at 12:41 PM

I'm going to reiterate that I think further argumentation is not useful until we can actually read the study.

NiroZ said:
Those links don't say that.

I disagree.

NiroZ said:
I feel like you're shooting the messenger here for something they're not even saying. What exactly do you think I'm trying to achieve by posting this study?

Your intentions are irrelevant. The study's conclusions are the topic of discussion.

NiroZ said:
that a adult microbiome does not allow new species into the microbiome without FMT

Of course it does. You're missing the "host-native microbes that have been evolving alongside us for millions of years and get passed down generationally", which I mentioned and cited previously.

NiroZ said:
I'd also suggest you add this study to the guide

It's already there.

NiroZ said:
How do you feel about my point that eating a diet that is healthy for you is harmless thing to try in order to recover from antibiotics?

Everyone should be eating a healthy diet regardless. If you want to say this study shows that eating an unhealthy diet exacerbates the damage from antibiotics, I would fully agree with that. However, that is not their conclusion/claim. Suggesting that a healthy diet alone is sufficient to reverse the damage from antibiotics is dangerous misinformation that is heavily contradicted by a huge body of evidence, which I cited.

Diet outperforms microbial transplant to drive microbiome recovery in mice (April 2025) Diet

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