August 30th, 2024

A primer on why microbiome research is hard

Microbiome research has progressed slowly despite significant investment, facing challenges in characterization, interpretation of advanced sequencing methods, and establishing causal links to health, though fecal transplants show promise.

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A primer on why microbiome research is hard

Microbiome research has gained attention over the past two decades, particularly following the discovery of the role of H. Pylori in peptic ulcers, which highlighted the microbiome's connection to various health aspects. Despite significant funding and numerous studies, progress in the field has been slow, primarily due to the inherent complexities of studying microbiomes. Characterizing microbiomes is challenging because of their vast diversity and the dynamic nature of microbial ecosystems. Traditional methods like 16S sequencing have limitations, leading to the adoption of more advanced techniques such as shotgun metagenomic and metatranscriptomic sequencing. However, these methods also face issues, including difficulties in interpreting results due to the vast number of uncharacterized species and potential biases in data analysis. Establishing causal relationships between microbiomes and health conditions is another significant hurdle, as variations in microbiomes can be influenced by numerous factors, including diet and lifestyle. While fecal microbiome transplants have shown promise in treating specific conditions, the broader application of microbiome research remains complicated. Overall, the field continues to grapple with the challenges of accurately characterizing microbiomes and understanding their functional impacts on human health.

- Microbiome research has made limited progress despite significant investment and interest.

- Characterizing microbiomes is complicated due to their diversity and dynamic nature.

- Advanced sequencing methods have improved analysis but still face interpretation challenges.

- Establishing causal links between microbiomes and health conditions is difficult.

- Fecal microbiome transplants represent a successful application but are not widely used.

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Link Icon 6 comments
By @zug_zug - 5 months
Fascinating article.

Slightly-off-topic:

This article presents the hard science as exceedingly difficult. I kinda suspect part of that is scientists have this attitude of acting completely blind to the hundreds of millions of years of evolution that made us what we are.

For example, if we suppose that microbiome is important to health, and suppose that all human behaviors (e.g. hand-shaking, kissing) I think it gets us pretty quickly toward some great avenues to test. I almost wonder if the imperfect sanitation conditions we evolved in might have conferred some ability to exchange fecal microbes.

Now obviously this doesn't really solve the fact that sequencing a microbiome is incredibly hard. But even without sequencing a microbiome you could probably do a blind test of saliva-swapping vs water and see to what degree this affects self-reported measures. Or if that's too hard to get past IRB, have one towel that's been touched by 50 people and one towel that's completely clean, and see if touching that has any subjective effects.

It feels like the kind of things you could test on 1,000 students in a weekend for free.

By @doodlebugging - 5 months
Thanks for this article. I think it places a lot of the gut microbiome studies and findings in context.

As a note for the author in case they are reading - you should do a quick Find/Replace on the article keyed on the word "git". There is more than one instance in the text where it clearly should read "gut microbiome" (or similar) and instead reads "git microbiome".

By @Metacelsus - 5 months
Regarding the cancer microbiome controversy, I am on the side of the skeptics. The issue of mis-identifying human sequences as bacterial (due to human DNA contamination in bacterial reference genomes) is a big problem, and the authors of the original study didn't properly filter out human-derived sequencing reads. That error, by itself, invalidates the paper.
By @bn-l - 5 months
Thanks for the link. Very important research and I’m thankful for the scientists taking it on.
By @lencastre - 5 months
More like this please!!!
By @PaulHoule - 5 months
I kinda roll my eyes when I hear anything about the microbiome because it so rarely turns into an actual therapy.