マイクロバイオームの神話

Hello and thanks for listening in. Welcome again to Biomes, the microbiome podcast. My name is Dr. Rory Robertson and over the last few months I have had the pleasure of chatting with some of the world's leading microbiome scientists. And this week we have a double whammy with two guests joining together and the topic is slightly different to other episodes. Have you ever heard facts such as there are 10 times as many bacterial cells in your body as human cells, or your gut microbiome weighs two kilograms, the same weight as your brain, or there is a placental microbiome interacting with the fetus? Many of these statements have been used for years in discourse surrounding the microbiome and I myself have used them regularly. However, as the microbiome field has progressed, a number of mythbusters have addressed these popular claims with actual science and found that some of them are only somewhat true, whilst others are total myths. As the field of microbiome research is so new and has so much hype, it is at risk of becoming entrenched with falsehoods and claims that aren't backed by scientific evidence. This is why it's critical that we address these myths to ensure that the true, exciting evidence about the microbiome can be communicated effectively. This week I speak to two of the loudest voices in microbiome mythbusting, Professor Alan Walker of the University of Aberdeen and Professor Jens Walter from APC Microbiome Ireland in University College Cork. Alan and Jens have published several papers setting the record straight on various dubious microbiome claims and ensure that scientists and microbiome enthusiasts don't get ahead of themselves with sensationalist statements. Despite their extensive mythbusting, they're still extremely enthusiastic about the potential for microbiome research to yield new discoveries in human medicine and continue to conduct their own research in this field. Thanks very much, Alan and Jens, for agreeing to chat all about myths of microbiome science because I think it's quite a hot topic in the field and we're going to go through some of these kind of pervasive myths that really dog not only the general public's thoughts on microbiome science but also us researchers as well and we are sometimes the ones who perpetuate them. So let's just start off, if you could both kind of just give a little introduction to who you are and what you work on and how you got into microbiome science. So Alan, do you want to start off and tell us who you are? Yeah, thanks, Rudy. So I'm Alan Walker, I am a gut microbiologist, I've been working on gut microbiomes for over 20 years now and I work up at the Rowat Institute at the University of Aberdeen and we are mostly interested in how what we eat impacts the gut microbiome and then in turn how that impacts our health but we also do various other research looking at how our microbiome protects against pathogens both in humans and in animals and basically anything functional. We really want to work out what these bugs are doing so as well as sort of profiling and using these modern sequencing approaches, we also do a lot of sort of in the lab based work with the bacteria to try and mechanistically work out what some of these little microbes are doing in our guts. So yeah, varied research, been doing it a long time, it's enjoyable stuff. Right. And Jens. Hi. Thanks for having me. So I'm Jens Wolter, I'm with the APC Microbiome Island and University College Cork here in sunny Southern Ireland. I'm also in this field for quite a while, like Ellen, so I'm a microbiome researcher for probably now 23 years, interested in how gut microbes evolve and I'm interested in kind of basic ecological principles that shape microbiomes and then I try to apply this to modulate microbiomes and I'm interested in microbial based modulations like probiotics and FMTs but I'm also interested in dietary modulations and using diet and nutrition and prebiotics and fiber, you know, to achieve some, you know, rational modifications to microbiomes and this is probably where Ellen and I overlap the most and have also overlapped the most in the last, you know, it goes back 15 years, I remember when we ran into each other on a conference where we had essentially the same poster. So yeah, pleasure to be here and to have that conversation. Great. So you're both kind of, I think, well renowned for trying to bust a lot of these myths that persevere in the microbiome world, both in the public realm but also in the kind of professional realm, I guess, if you want to call it that, within the community of microbiome researchers. So we're going to run through maybe four or five of these more prevailing myths. So Allen, you know, recently wrote a paper on this in Nature Microbiology, kind of going through each of these myths one by one and busting them, whereas Jens is well known for busting the myth of the placental or fetal or prenatal microbiome which we'll touch on. So maybe, Allen, I can start with you. The first myth that we're going to discuss is that microbiome research is a new field. We all like to say that to kind of make it out we're these big pioneers, you know, and we're doing something that's cutting edge and really new. But, you know, microbiology research has been going on for years, yeah, you know, for centuries since Anthony von Lohenhoek, you know, saw microbes under a microscope and Metchnikoff, you know, discovered the role of some commensal organisms. So maybe you can talk us through that a little bit, the history of microbiome research and why that is a myth that it's very new. Yeah, no, definitely. So, I mean, you're quite right to pinpoint Anthony von Lohenhoek. He's the first one to ever see a microbe under a microscope. That was hundreds and hundreds of years ago. You know, microbiology as a field really kicked off with pioneers like Louis Pasteur, which people will have heard of, I'm sure, and, you know, just working out the roles that microbes played in disease. That goes back well over 150 years. I think if you look into something like E. coli, it was first isolated back in the late 1800s as were bifidobacteria, these very beneficial microbes associated with health and babies. And so, you know, this is well over 100 years ago, people were doing very valuable, vital microbiome research. I mean, I'll be honest, it was much more of a cottage industry for a long time. And so when I was doing my PhD back in the early 2000s, I think you got maybe one paper a month at Lucky and, you know, in the rumen microbiome of the cow, you were excited because at least it was a gut paper. And then I think I checked last year, it was well over 1000 papers every month. So, you know, it's undeniable that the field has completely gone crazy. You know, there's been a huge revolution, which is underpinned by modern molecular methods to study microbes. But it's not a new field. It goes back many, many, many decades. And I think the thing that really got my goat a little bit was, you know, when we talk about it being a new field, we actually do a disservice to lots of really, really nice work that was done before the advent of these modern sequencing approaches we use. So really, it was just an attempt to correct a record on that, to pay homage to some of the really pioneering researchers that came before us and, you know, just acknowledge that, you know, although we might like to claim a revolution, like you say, we are standing on the shoulders of quite a lot of giants. If I could add to this, you know, I've been, I fully agree, you know, and some of this is even real microbiome science, you know, I've just had to read up on early life microbiome for a review I was writing, you know, and so I read a few review papers, you know, that cited some of this early work by Tissier on Bifidobacteria and formula feeding and it was him and also others, you know, they seriously already knew that, you know, formula fed infants have more diverse microbiomes, you know, which is actually, I've just seen being presented in recent, I think even in titles of recent papers, you know, it's something new, you know. So this is, these guys with their microscopy, you know, found this out 120 years ago, you know, and I think, and then it continues on with all the germ-free work, you know, which goes back, I think, to the 60s, you know, where obviously this was designed, you know, to establish the causal role, you know, of microbiomes and then we had notobiology where we put specific microbes into mice, you know, again, 70, 80 years ago. So this was real microbiome research and some of these findings stand and I'm actually sometimes, you know, I'm, yeah, fascinated and sometimes even embarrassed, you know, when I realize something that I thought is novel and I wrote in a paper and then I find out Rainier Dubos, you know, I wrote on the evolution of lactobacilli, for example, and did a lot of population, you know, genomics, you know, to figure out how these microbes evolve and then I look back into an old Rainier Dubos paper from 60 and saw actually the final conclusion of my 10 years of work actually essentially being articulated there, you know. So, yeah, as Eran said, you know, it's worth to look back, give these giants credit, you know, but also, you know, we can learn something, you know, and methods that they've used, microscopy and, you know, germ-free technology, you know, they are still very, very valid, you know, they are really not outdated. Yeah, I totally agree. How much of this is down to the fact that we now have a term for it? You know, this term microbiome is, you know, if you put it in the title of a scientific paper, that seems to bump you up in terms of how much it's read and the interest in it, but the same in the public realm as well, you know, people who have no interest in science before will have probably heard of the term microbiome and mainly its links with gut health. So is that the reason that we think that it's a modern science or what is it about this term microbiome that has created or fed into this kind of revolution per se? Yeah, I would say, yeah, I think branding does help a little, I can't deny it, you know, I think, but I do just think it is a, it's a by-product of just the increasing interest that come from scientists, you know, it's, you know, one paper a month to a thousand papers a month, you're learning a lot more, right, in that time. Now, okay, we knew a lot already, but you are exponentially increasing what is known and every time something, you know, landmark happens and something exciting, it builds to that sort of snowball of excitement as it rolls down the hill. And so it becomes obvious, right? So I do think, you know, yeah, the branding helps a little and microbiome is something that I think the general public are able to latch onto as a concept, but I just think it's a virtue of just how much work has been done in the field now, you know, something new is happening all over the world every day and, you know, it captures the attention. So I do think it's just, it reflects the effort.

こんにちは。マイクロバイオームのポッドキャスト、Biomesへようこそ。私はローリー・ロバートソン博士で、この数ヶ月間、世界有数のマイクロバイオーム研究者たちとおしゃべりする機会に恵まれました。そして今週は、2人のゲストをお招きしてのダブルパンチで、トピックも他のエピソードとは少し異なります。体内に存在する細菌細胞の数は人間の細胞の10倍であるとか、腸内マイクロバイオームの重さは脳と同じ2キログラムであるとか、胎児と相互作用する胎盤マイクロバイオームが存在するといった事実を聞いたことがあるだろうか。このような文言の多くは、マイクロバイオームをめぐる言説で長年使われてきたものであり、私自身も常用してきた。しかし、マイクロバイオーム分野の進展に伴い、多くの神話バスターがこれらの一般的な主張を実際の科学で取り上げ、その中には多少正しいものもあれば、全くの神話であるものもあることが判明した。マイクロバイオーム研究の分野は非常に新しく、誇大広告が多いため、科学的根拠に基づかないデマや主張が定着する危険性がある。だからこそ、マイクロバイオームに関する真実でエキサイティングなエビデンスを効果的に伝えるために、こうした神話に対処することが重要なのです。今週は、マイクロバイオーム神話潰しの第一人者であるアバディーン大学のアラン・ウォーカー教授とコーク大学のAPCマイクロバイオーム・アイルランドのイェンス・ウォルター教授にお話を伺った。アランとイェンスは、様々な疑わしいマイクロバイオームの主張を正す論文をいくつか発表しており、科学者やマイクロバイオーム愛好家がセンセーショナルな発言で先走らないようにしている。彼らは神話を広範に破壊しているにもかかわらず、マイクロバイオーム研究がヒトの医学に新たな発見をもたらす可能性について非常に熱狂的であり、この分野で独自の研究を続けている。アランさん、イェンスさん、マイクロバイオーム科学の神話についてお話してくださってありがとうございました。この分野ではかなりホットなトピックだと思いますので、一般の人々のマイクロバイオーム科学に対する考えだけでなく、私たち研究者にも浸透している神話をいくつかご紹介します。それではまず、お二人がどのような方なのか、どのような研究をされているのか、そしてどのようにしてマイクロバイオーム科学の世界に入られたのか、少しご紹介いただけますか？アラン、まずはあなたがどんな人なのか教えてくれますか？ルディ、ありがとう。私はアラン・ウォーカーで、腸内細菌学者です。もう20年以上腸内細菌叢の研究をしていて、アバディーン大学のロワット研究所で研究をしています。腸内細菌が何をしているのかを解明したいので、プロファイリングや最新のシークエンシング・アプローチを使うだけでなく、腸内で小さな微生物が何をしているのかをメカニズム的に解明するために、細菌を使った実験ベースの研究もたくさん行っている。そうだね、いろいろな研究があるし、長いことやっているから楽しいよ。そうだね。そしてイェンス。こんにちは。お招きいただきありがとうございます。私はイェンス・ウォルターで、APCマイクロバイオーム・アイランドと、ここ陽光降り注ぐ南アイルランドのコーク大学にいます。腸内微生物がどのように進化していくのかに興味があり、マイクロバイオームを形成する基本的な生態学的原理にも興味があります、 エレンと私が最も重なり合うのはおそらくこの部分であり、過去15年間でも最も重なり合った部分でもある。だから、ここでこうして話ができて嬉しいよ。素晴らしい。お二人とも、マイクロバイオームの世界で根強く残る神話を打ち破ろうとしていることでよく知られていると思います。そこで、4つか5つ、より一般的な神話をご紹介しましょう。アレンは最近『ネイチャー・マイクロバイオロジー』誌に論文を書き、これらの神話を一つずつ検証し、それを打ち破った。ではアレン、あなたから始めましょうか。最初にお話しする神話は、マイクロバイオーム研究は新しい分野だということです。私たちは皆、自分たちが大きなパイオニアであり、最先端の、そして本当に新しいことをやっているのだと誇示するために、そう言いたがります。アンソニー・フォン・ローエンフックが顕微鏡で微生物を見て、メチニコフが常在菌の役割を発見して以来、微生物学の研究は何世紀も続いてきたんだ。では、マイクロバイオーム研究の歴史と、それが非常に新しいという神話である理由について、少しお聞かせいただけますか？ええ、もちろんです。つまり、アンソニー・フォン・ローエンフックという人物を挙げるのはとても正しい。顕微鏡で微生物を見たのは彼が初めてです。何百年も前のことだ。微生物学という分野は、ルイ・パスツールのようなパイオニアによって始まった。その歴史は150年以上にさかのぼる。大腸菌を調べてみると、最初に分離されたのは1800年代後半で、ビフィズス菌のように健康や赤ちゃんに関連する非常に有益な微生物だった。つまり、100年以上も前に、人々は非常に貴重で重要なマイクロバイオーム研究を行っていたのです。正直に言うと、それは長い間、家内工業的なものでした。私が博士課程に在籍していた2000年代初頭には、ラッキーなことに月に1本くらいのペースで論文が発表されていたと思います。しかし、昨年確認したところ、毎月1000以上の論文が発表されていました。つまり、この分野が完全に狂ってしまったことは否定できない。微生物を研究する最新の分子学的手法に支えられた大革命が起きているんだ。しかし、これは新しい分野ではない。何十年も前のことだ。新しい分野だと言うとき、私たちが使っている近代的なシーケンサーが登場する前に行われた、本当に素晴らしい研究に対して失礼になる。私たちは革命を起こしたと主張したいかもしれませんが、あなたが言うように、私たちは多くの巨人の肩の上に立っているのです。そして、その一部は本当のマイクロバイオーム科学でもある、 その論文では、ビフィズス菌と粉ミルク栄養に関するティシエの初期の研究が引用されていて、彼や他の研究者たちは、粉ミルク栄養の乳児のマイクロバイオームがより多様であることをすでに知っていた。顕微鏡を使ったこの研究者たちは、120年前にこのことを発見したのですが、その後、無菌の研究が続いています。私は、自分が斬新だと思って論文に書いたことが、レイニア・デュボスが乳酸菌の進化について書いたものであることを知ったとき、とても驚きますし、時には恥ずかしくさえなります、 例えば、私は乳酸菌の進化について書いていて、これらの微生物がどのように進化していくのかを解明するために、集団、つまりゲノミクスをたくさん行った。だから、エランが言ったように、振り返って、この巨人たちに敬意を表する価値がある。ああ、まったく同感だ。微生物学という用語ができたことで、どれだけの影響があるのでしょうか？このマイクロバイオームという言葉は、科学論文のタイトルに入れれば、その論文の読まれ方や関心の度合いが上がるように思えますが、一般の領域でも同じで、これまで科学に関心のなかった人たちも、マイクロバイオームという言葉や、主に腸の健康との関連については耳にしたことがあるでしょう。では、マイクロバイオームが現代科学だと思われているのはそのためなのでしょうか？それとも、マイクロバイオームという言葉がこのような革命そのものを生み出した、あるいはもたらしたのでしょうか？そうですね、ブランディングは少しは役に立っていると思いますし、否定はできませんが、科学者の関心が高まっていることの副産物だと思います。そして、何か画期的なことが起きたり、エキサイティングなことが起きたりするたびに、雪だるま式に興奮が高まっていく。そうすれば、それは明白になる。マイクロバイオームというのは、一般の人たちが概念としてとらえることができるものだと思います。だから、その努力が反映されているのだと思う。