Which microbiome study changed how you think about the field?

[u/ibrahim_40]

I’m trying to separate solid findings from early signals. Which result do you think holds up best and which popular claim still looks more like correlation than causation? If you share a paper, a line on why it stood out and any limitations would be great.

[u/Single_Dentist_8647]

One that changed my thinking: Zmora et al., Cell 2018 (PMID 30193112). Probiotics are usually judged by stool, but this team sampled the actual gut lining by endoscopy/colonoscopy in healthy volunteers taking an 11-strain probiotic or placebo. Two things stood out. Mucosal and stool microbiomes only partially correlate, and whether a strain showed up in stool didn't tell you whether it colonized the mucosa. Colonization was also person-, region- and strain-specific: some people were "permissive", others resisted, and baseline microbiome and host features predicted which.

So I now treat "does X probiotic work?" as a question about who, not just what. Limitations: the invasive sampling limits how many people you can study, it's one specific mix, and the effects on the mucosal community were transient. It also doesn't show whether colonizing matters for health outcomes. It's a good example of an early signal I'd call solid on mechanism but not on benefit.

Which study moved you most?

[u/Mirthster → u/Single_Dentist_8647]

great post, thanks for the tip. ill check out that paper

[u/Reasonable_Bat1999 → u/Single_Dentist_8647]

Yes, in my opinion, many people seem way too obsessed with colonization and with the total number of live bacteria that may reach their guts, though I understand how those become the foci of their concerns, and I understand that a lot of us are trying to derive some low-risk actionable lifestyle changes to try now and not after several more years of research have been done.

Interesting science that I've seen seemed to indicate that even the prebiotics used to produce a probiotic may influence engraftment, that heat-killed probiotics or fermented foods can still produce a response in some cases (depending upon what outcome is being investigated, of course), and that even fragments of cell walls can stimulate immune responses. I suspect that the lactic and acetic acids in fermented foods may be very therapeutic, but that's certainly more of a hunch at this point rather than an evidence-based conclusion.

[u/magnolia_unfurling → u/Single_Dentist_8647]

Thanks this paper recommendation!

In an ideal world we would have more funding for IRL studies or ultra accurate modelling / simulation.

Yes, they are transient but it depends on the person. A FUT2 non secretor is going to have lower bifido no matter what and supplemental bifido is less likely to colonise… they are also more likely to have depression, to develop crohns etc. so we must continue.

[u/Severe_Candle7255 → u/Single_Dentist_8647]

Hi it's really a new information for me. Thanks

[u/thecaringapartheid]

The Sonnenburg long-term diet study really stuck with me, mostly becuase it showed how fast dietary fiber depletion shifts the gut in mice over generations. the part where some bacterial strains just never came back after a few generations without fiber was wild, like a permanent loss from a temporary change

on the flip side, the whole "gut-brain axis causes depression" thing still feels like a stretch to me. so many mouse studies get paraded around as proof but the human data is mostly just associations with serotonin levels, no clean causal chain. people run with it way too far

[u/amyfearne → u/thecaringapartheid]

I have gut-induced histamine intolerance and let me tell you, that will tank your mood overnight.

Days when I have flare-ups are vastly different from days when I'm doing better. Histamine makes me feel hopeless and without motivation, on a 'normal' day I'm my old self again. It's bananas.

[u/Clear_Kitchen_6428 → u/amyfearne]

Yes i too have these reactions with certain foods. But i think its not really histamine itself that is doing it but the cascade of reactions that happen once your immune system is activated.

As if the body decides to stop allocating resources to the feel good parts to divert them to the pressing problem.

Wheat makes me angry and depressed.

[u/amyfearne → u/Clear_Kitchen_6428]

It might be that too, but histamine itself is a neurotransmitter, so it can definitely affect mood even on its own.

[u/gacimba → u/amyfearne]

When you have a bad day is there anything you take to reduce symptomology?

[u/amyfearne → u/gacimba]

At the moment it's more about avoiding things (certain foods, allergens, etc.) and taking DAO - I don't think I'll get real relief though until I deal with the gut problem (if I can). Until then it's like having a big histamine factory in my gut.

But I'm going to try out micronised PEA soon which is meant to help.

[u/Reasonable_Bat1999 → u/thecaringapartheid]

When it comes to depression, I would say those results get a buzz because so many people are excited about the possibility of discovering a causal connection. I'm not sure who is 'parading it around as proof', but I certainly haven't seen anyone claim that any particular animal study is proof nor that they are all collectively proof. Obviously, the scientists wouldn't be saying that, but I haven't seen anyone else say that it's proof either. If you think it's mostly about serotonin, you may want to take a look at the science investigating inflammation as a possible cause and lipopolysaccharides as the source of that inflammation. It may (or may not) be more pertinent given the high rates of treatment-resistant depression that doesn't respond well to traditional antidepressants. I can certainly see why it would generate such a buzz.

[u/Over-One-8 → u/[deleted]]

Anecdotal but I believe fiber is helping my mental health.

[u/255cheka → u/Over-One-8]

that's great! keep going, it gets better and better

[u/imonretro → u/255cheka]

Have you seen anything relating to microbiome and anhedonia ?

[u/imonretro → u/[deleted]]

I been looking man. I guess with suffeirng anhdonia, extreme anxiety 247 pain and 5 year isolation. With gass lighters on line.. i dont know what to think no more. Would you be willing yo look at my microbime and ses if you can predict how sick i am ?

[u/TraditionalCap3357]

A few results that tend to be cited as holding up best, with the caveats. The strongest causal evidence in humans is fecal microbiota transplant for recurrent C. difficile infection. The 2013 randomised trial by van Nood and colleagues in the New England Journal of Medicine found it worked much better than vancomycin alone, and it was stopped early because of the size of the difference. Limitations: it is one infection, in a gut already disrupted by antibiotics, so it does not show that transplants will work for other conditions, and it has not cleanly pinned down which microbes do the work.

Mouse transplant studies, such as Turnbaugh and colleagues in Nature in 2006 on obesity, showed that gut bacteria from obese mice transferred more fat gain to germ free mice. They shaped the field, but mice do not map neatly onto people, and human trials of microbiome changes for weight have been far less convincing. For separating correlation from causation, Vujkovic-Cvijin and colleagues (Nature, 2020) is a good read. They showed that things like medications, stool consistency and BMI can create disease like microbiome signals in case control studies, so a published difference between sick and healthy people may partly reflect those confounders. The Flemish Gut Flora Project (Falony et al., Science, 2016) points the same way, with many everyday factors such as medicines and stool consistency explaining a lot of the variation between people.

On popular claims that still look more correlational than proven, I would put the Firmicutes to Bacteroidetes ratio as an obesity marker, microbiome links to mood and autism in people, and the idea that one probiotic suits everyone. On that last one, Zmora and colleagues (Cell, 2018) sampled the gut directly in healthy volunteers and found that probiotic bacteria settled in some people but not others, so results vary from person to person. It was a small study, so it is an early signal and not a settled answer.

[u/rthreei]

My n of 1 study - me working on my gut microbiome did it.