肠道感知科学与肠脑轴 | Diego Bohórquez博士

他们会随订单赠送五包旅行装，外加一年的维生素D3K2。

They'll give you five free travel packs with your order, plus a year supply of vitamin D3K2.

再说一次，网址是drinkag1.com/huberman。

Again, that's drinkag1.com/huberman.

好，你确认了这些细胞，你说是描述，但我会说是发现，因为事实就是这样。

Okay, so you identified these, you said described, but you I'll say discovered because that's what happened.

你发现了这些细胞，标记了它们的连接，看到这些细胞和大脑之间只有两个中转站，或者说其实只有一个中转站。

You discovered these cells, you label their connections, you see that there's just two stations between these cells or one station really between these cells and the brain.

所以现在这些细胞能感知肠道里因食物分解产生的化学物质，并把信息直接传给大脑。

And so now these cells can sense chemicals in the gut that are the consequence of the breakdown of food and send that information directly to the brain.

大脑会怎么处理这些信息呢？

What does the brain do with that information?

接下来就是关键实验了。

So here comes the key experiment.

这显然是建立在其他科学家的工作基础上的，他们已经发现肠道里有糖的受体，特别是葡萄糖的，还有其他营养素的受体。

And this was building obviously on the work of other scientists that had already described that the gut had some receptors for sugars, specifically for glucose, for other nutrients.

大概在2000年代初期，我们开始能够识别这些细胞的时候，很快就发现这些肠内分泌细胞遍布胃、肠道和结肠的内壁，它们有多个受体来感知多种营养物质。

Around this area in the early 2000s when we were starting to be able to identify some of these cells, then it quickly became obvious that these cells, these enteroendocrine cells, throughout the lining of the stomach intestine colon, they had multiple receptors for multiple nutrients.

你知道，就像我们说的宏量营养素，比如糖、脂肪、蛋白质。

You know, like we have the macronutrients, for instance, sugars, fats, proteins.

但其中包含了很多种不同的分子。

But within them we have a repertoire of molecules.

多种脂质、多种糖类等等。

Multiple lipids, multiple types of sugars and so on and so forth.

这些细胞根据它们所在的位置，会表达不同类型的受体，或者这些受体的组合。

And these cells, depending on their location, they will express a different type of receptors or a combination of those receptors.

我说取决于位置，是因为当我们吃东西的时候，比如吃一个苹果，苹果在进入肠道的时候可能还没有完全消化。

And I say that depending on the location because when we're eating, let's say an apple, you know, apple is going to be partially undigested by the time that it enters intestine.

但等它到达结肠时，大部分营养物质已经被吸收了，可能只剩下纤维，用来喂养结肠里的微生物，对吧？

But by the time that it gets to the colon, most of those nutrients are being absorbed and perhaps only fibers are surviving to feed off most of the microbes that live in the colon, right?

所以，肠道已经进化得能够镜像并像魔术贴一样，吸附那些特定空间里存在的分子。

So, the gut has evolved to mirror and to become a Velcro to the molecules that will be in that specific space.

所以，肠道在近端小肠会更敏感地检测糖分，而在远端小肠或结肠则更关注纤维或发酵产物，比如短链脂肪酸、丁酸、丙酸等等。

So, will detect sugars more in the proximal intestine, but fibers or fermented byproducts more in the distal intestine or in the colon, like short chain fatty acids, butyrate, propionate, and so on and so forth.

这些神经足细胞还能从食物中检测到哪些其他类型的营养素？

What other kinds of nutrients do these neuropod cells detect from food?

你提到了糖和发酵，那是不是也检测短链和长链脂肪酸呢？

So you mentioned sugars, you mentioned fermentation, so presumably short and long chain fatty acids?

是的，简单来说，我觉得随着时间推移，我们会发现它们几乎能检测我们每天吃进去的所有东西。

Yes, the short answer is that, I think that in due time we are going to realize that they detect just about every single thing that we put on our mouths every day.

它们要么有专门针对某种化合物的特定受体，要么通过多种受体的组合来识别这些物质。

That they have some either a specific receptor that is dedicated to it or a combination of receptors to be able to detect some of these compounds.

而且不仅仅是化学物质，我觉得未来一个很吸引人的领域是，当食糜从口腔流向结肠时，它们还能感知机械扩张和温度变化。

And not only the chemical compounds, but also an area that I think is going to be fascinating in the future is the mechanical distention plus the adjustment in temperature as the chyme starts to flow from the mouth into the colon.

比如，不久前我听到一位生物工程师提到，他在设计人造肠道和胃。

Like for instance, I heard this from a bioengineer not long ago that was engineering artificial gut and stomach.

他告诉我一个我之前不知道的信息：食道需要在几秒钟内迅速将食物温度调节到体内的生理温度。

And he shared with me a piece of information that I was not aware of that the esophagus has to adjust the temperature of the food very rapidly within seconds into physiological temperature of the inside of the body.

比如说，如果我们喝热咖啡，几秒钟之内，它到达胃里的时候就得降到身体的生理温度，对吧？

Like, so if we're having hot coffee, within couple of seconds it has to be at the physiological temperature of the body by the time that it gets into the stomach, right?

而且这一切都发生得非常快。

And all of that happens very rapidly.

太神奇了。

Amazing.

而且它还挺受罪的，对吧？

And it suffers, right?

如果我没理解错的话，这些神经足细胞有各种各样的受体，对吧。

If I understand correctly, these Neuropod Cells have a variety of different receptors, Correct.

它们分布在从口腔到直肠的整个路径上，位置不同，功能也不同。

Depending on where they are located along the trajectory from the mouth to the rectum.

没错。

That's correct.

有些感知糖分，有些感知温度，有些感知pH值，也就是相对酸度。

And some are sensing sugar, some are sensing temperature, some are sensing pH, so relative acidity.

有些细胞大概是在感知氨基酸。

Some are sensing amino acids, presumably.

我是说，我听过这种说法，而且我相信澳大利亚有一位研究员，他一直非常看好这个理论，认为我们不是完全依赖氨基酸，但主要是靠寻找氨基酸来维持生存的机器，因为我们需要氨基酸来进行各种重要的生物过程。

I mean, I've heard it said, and I believe there's a researcher down in Australia who's been very bullish on the theory that we are not exclusively, but we are predominantly amino acid foraging machines because we need amino acids for all sorts of important biological processes.

这些细胞基本上在评估有多少糖、多少亮氨酸、多少短链脂肪酸、多少不同种类的必需脂肪酸，然后对肠道本身做出调整，但大概也会把那些信息传递到身体的其他部位。

And these cells are essentially evaluating how much sugar, how much leucine, how much short chain fatty acid, how much essential fatty acids of different kinds and then making changes to the gut itself, but then presumably signaling that information elsewhere in the body.

那么，接下来我要给你讲点东西，可能会让你的肠胃翻腾起来，可以这么说。

So, here I'm gonna give you something that will get your gut churning, so to speak.

所以，这些细胞不仅要理解摄入的分子，也就是分子的化学性质。

So, these cells have to make sense not only of the molecule that had been ingested, meaning the chemistry of the molecule.

比如说如果是葡萄糖，它还得稍微理解一下味道。

Let's say if it's glucose, it has to make sense a little bit of the taste.

甜不甜？

Is it sweet?

对吧？

Right?

苦吗？

Is it bitter?

然后它还得考虑有多少分子被细胞吸收了。

Then it has to take into account how much of the molecule is absorbed inside of the cell.

对吧？

Right?

所以这是第二层的整合。

So that's the second layer of integration.

然后，一旦细胞“吃掉”了那个分子，那个分子就会在细胞内部被消化，释放出ATP或其他化合物。

Then once the cell has eaten that molecule, so to speak, then that molecule will be digested inside of the cell to release ATP or some other compound.

ATP就是用来提供能量的，比如。

ATP is for energy, for instance.

这一点也得考虑进去。

That has also have to be taken into account.

比如说，对于葡萄糖来说。

For instance, in glucose.

葡萄糖会激活TAZ1R3，这是一种甜味受体。

Glucose activates the TAZ1R3, which is a sweet taste receptor.

然后葡萄糖被一些钠葡萄糖转运体吸收，这些转运体是主动转运体。

Then the glucose is absorbed by some of these sodium glucose transporters, which are active transporters.

这些转运体会使细胞去极化。

And these transporters depolarize the cell.

一旦葡萄糖进入细胞，它进入三羧酸循环，被分解代谢，然后产生ATP。

And then once glucose gets inside of the cell, glucose enters the TCA cycle, is catabolized, then produces ATP.

ATP进一步激活另一个电压门控通道，使细胞进一步去极化。

And the ATP further activates another voltage gated channel, farther depolarizing the cell.

然后细胞释放一种递质，比如谷氨酸，它能在几毫秒内迅速告诉迷走神经：我这里有糖。

And then the cell releases in turn a transmitter, for instance, glutamate that very rapidly tells the vagus nerve within milliseconds, you know, I got sugar.

它分两个阶段传递这个信息，因为谷氨酸会激活两种不同类型的受体。

And it tells it in two phases, because that glutamate will activate two different type of receptors.

一种是离子型受体，反应非常快；另一种是代谢型受体，反应稍慢一些。

Ionotropic, which are very fast, and metabotropic, which are a little bit more delayed.

但是，葡萄糖代谢产生ATP，进一步使细胞去极化，我们认为这会导致激素和神经肽的释放。

But then, the metabolism of that glucose that produces ATP and further depolarizes the cell, we believe that it will cause the release of the hormone, of the neuropeptide.

所以，神经肽在此基础上叠加，给你带来完整的糖分摄入体验，对吧？

So, the neuropeptide comes on top of that and gives you that full experience of what it means to consume sugar, right?

所以，这一切发生在一个细胞和一个分子的层面上。

So, that happens at the level of one cell and at the level of one molecule.

所以，肠道必须对消化道中的每一个分子进行所有的计算。

So, all of the computation that the gut has to be making for each one of the molecules throughout the digestive tract.

所以，如果我从这个画面退后一步，我看到的是，排列在我们肠道中的非常有趣的细胞类型，它们不仅评估宏量营养素，如蛋白质、脂肪和碳水化合物，还评估我们食物中的微量营养素，以及一些其他定性特征，比如温度，甚至可能评估氨基酸或糖的质量，以及复合糖等。

So if I stand back from this picture, what I get is there are very interesting cell types that line our gut that are evaluating all of the, not just macronutrients, proteins, fats, and carbohydrates, but micronutrients within the food we eat, as well as some of the other qualitative features, temperature, for instance, maybe even quality of the amino acids or the sugars, versus complex sugars, etcetera.

如果我们能再稍微拉远一点，从人类体验的角度来看待这个问题。

If we could just further zoom out for a moment and take a human perspective on this at the level of experience.

我听过你讲过一个故事，关于你认识的一个人，他们彻底改变了肠道，从而改变了他们对食物的整个感知体验，包括某些渴望。

I once heard you tell a story about someone you knew who changed their gut radically and that changed their entire perceptual experience of food, including certain cravings.

你愿意分享那个故事吗？

Would you mind sharing that story?

是的。

Yes.

谢谢你提起这个故事，安德鲁。

Thank you for bringing that story, Andrew.

这个故事对我来说非常个人化。

That story is very personal to me.

我经常在台上说，生活中我们不断受到两件事的影响：我们吃的食物和我们遇到的人。

I often say when I get on stage that we are constantly influenced by two things in life, the food that we eat and the people that we meet.

你知道，就像我们现在已经认识了，但现在我们面对面见面，也在认识其他人，对吧？

You know, like, now we have known each other, but now we meet in person and we are knowing other people, right?

我记得我刚开始在北卡罗来纳州立大学攻读营养学博士学位时，我并不是在美国长大的。

And I remember that when I was starting my PhD in nutrition at North Carolina State University, I was, so I didn't grow up in The United States.

我在厄瓜多尔长大。

I grew up in Ecuador.

我被邀请去参加我的第一个感恩节庆祝活动。

And I was invited to my first Thanksgiving celebration.

所以，我坐在餐桌旁，你知道，当我们开始和旁边的人聊天时，我突然被一位女士的故事吸引住了，她跟我讲她做胃绕道手术来治疗肥胖的经历。

So, I sat at dinner and, you know, as we began chatting with the people that were next to each other, all of a sudden I was enthralled in this conversation of a woman telling me this story about her experience with gastric bypass surgery for treating obesity.

胃绕道手术是60年代由外科医生开始开发的。

So, bypass surgery was begun to be developed by surgeons in the 60s.

到了90年代，它已经成为治疗慢性肥胖的主流手术方式。

And by the 90s, it had become a mainstream type of surgery for the treatment of chronic obesity.

她告诉我，主要发生了三件事。

So she told me that there were primarily three things that happened.

她说，手术后六个月内，我减掉了大约40%的体重。

She said, well, within six months of the surgery, I had lost about 40% of body weight.

她说，我当时大概有三百磅重。

She said, I was about three hundred pounds.

你自己算算吧。

You do the math.

所以，那是一个

So, it was a

挺多的。

Significant amount.

对，挺多的。

Yeah, significant amount.

她说，手术一周后，我的糖尿病就好了。

She said, Within one week of the surgery, my diabetes was gone, she said.

我再也不需要打胰岛素了。

I did not need more insulin shots.

所以，我当时和你的反应一样。

So, I had the same reaction that you're having.

我就想，我对糖尿病了解不多，但我知道它是个很大的健康负担，对吧？

Was like, I don't know much about diabetes, but I know that it's a major health burden, right?

但真正让我注意的是，她说，既然你在研究营养学，我想让你回答我一个问题。

But the thing that really caught my eye was when she said, But, since you're studying nutrition, I want you to answer this to me.

她说，为什么手术前，我连看到煎蛋都受不了？

She said, Why is it that before the surgery, I could not even look at Sonny Side Up X?

她说，光是看到蛋黄就会让她觉得恶心。

She said, Just looking at the yolk will make me queasy.

但手术后，她不仅能吃太阳蛋，甚至还会特别想吃蛋黄。

But after the surgery, not only I can eat Sunny Side Up eggs, I actually have a craving for the yolk.

她说，每个星期六我们去餐厅吃早餐的时候，她都会拿吐司把盘子里的蛋黄擦干净吃掉。

She said, Every time we go on Saturday to a restaurant for breakfast, I will take the toast and I will actually clean the plate of the yolk.

她说，为什么重新调整肠道会改变她对味道的感知，改变她的渴望，让她的大脑想要蛋黄呢？

So, how is it that rewiring the gut altered my perception of flavor, altered my cravings and my mind to get the yolk, she said.

甚至把她对厌恶和食欲的感知也颠倒过来了。

And even inverted her sense of what was aversive versus appetitive.

我想，对于我们这些不了解的人来说，比如我，我理解胃绕道手术是切除一部分肠道。

And I guess for those of us that don't know, meaning me, I understand that gastric bypass surgery involves the removal of a portion of the gut.

他们到底切了多少肠道组织？

How much gut tissue do they actually take?

是几厘米还是几英寸？

Is it centimeters, inches?

对，不是。

Yeah, no.

我是说，肠道很长。

I mean, gut's a long distance.

那他们是怎么做的，

So, do they do for

胃绕道手术。简单来说，经典的手术叫Roux-en-Y胃绕道手术，就是缩小胃，并且把胃和肠子的连接改道，缩短路径。

gastric So, in simple terms, the classic surgery is called Roux en Y gastric bypass surgery, which involves a reduction of the stomach and short cutting the connection of the stomach to the intestine.

所以会切掉三分之一，也就是十二指肠。

So you will cut one third, which will be the duodenum.

那三分之一会被切掉，然后那部分会重新接到胃上，也就是说你是在给肠道短路。

One third of that will be cut and then that portion will be reconnected to the stomach, meaning that you're short circuiting gut.

最初的想法是，如果我们减少暴露在食物中的表面积，那么通过简单地减少吸收食物的表面积，就能减轻体重。

And the whole idea was, at the very beginning, was like, well, if we reduce the surface that is exposed to food, then we can reduce body weight by the simply reduction of surface that is exposed to the food that is absorbed.

对吧？

Right?

而且很快就发现，在体重变化发生之前，生理上就已经有了剧烈的变化，比如肠道在应对营养时释放的激素和神经肽。

And what it became very clear is that well before the body weight changes got taken place, there was already like some dramatic changes in physiology, like the hormones, the neuropeptides that were released from the intestine in response to nutrients.

这些变化来得非常快。

It will change very rapidly.

然后，就像我提到的，食物选择会改变，糖尿病也会得到缓解。

Then, as I mentioned, the food choices will change, diabetes will be resolved.

所以，很明显，这不仅仅是肠道表面积减少的问题。

So, then it became obvious that it was not necessarily just the reduction in the surface of the gut.

这是其中一种主要的手术。

So that's one of the main surgeries.

另一种，据我了解，是袖状胃切除术。

The other one, as I understand, is vertical sleeve gastrectomy.

这种袖状胃切除术其实就是缩小胃的尺寸。

And this vertical sleeve gastrectomy is simply a reduction in the size of the stomach.

这样一来，胃变得非常小，它的容量就小了，能装的食物少了，食物就会很快进入肠道。

So, now the stomach is very tiny and the idea is that it will accumulate less, it could hold less food and then the food will go very rapidly into the intestine.

而且很明显的一点是，胃肠道的感官功能发生了快速变化。

And what becoming very obvious is that there is a rapid change in the sensory function of the gastrointestinal tract.

所以肠道似乎迅速转变，可以说，总体上对营养物质的感知变得更敏感了，对吧？

So the gut seems to rapidly shift, perhaps become more, so to speak in general terms, more sensitive to the presence of nutrients, right?

有意思，所以你在感恩节遇到的那位女士做了胃绕道手术，而且我想可以合理推测，很多感知不同营养物质的神经足细胞都被切除了。

Interesting, so this woman that you met at Thanksgiving had gastric bypass surgery, and presumably, I think it's fair to assume a good number of these Neuropod cells that sense different nutrients were removed.

结果，她对某种食物的渴望完全改变了。

And as a consequence, she completely shifted her craving of a particular food.

那么，有没有可能，这里不是双关，她对溏心蛋蛋黄感知的缺失，跟食欲变化或者其他方面有关呢？

And is there any sense whether or not, no pun intended, the lack of sensing of what was in Sunny Side egg yolks was somehow related to a shift in appetite or something else?

还是说，这仅仅是对她渴望的东西的一种质变，虽然这种质变很显著？

Or is it merely a qualitative, albeit a dramatic qualitative shift in what she craved?

这里有两个背景信息。

So two contextual pieces of information.

我记得离开那顿晚餐时，我心里想，哇，这太重要了。

So I remember leaving that dinner and I was like, Woah, this is major.

我知道，我相信肯定有人写过相关文章或者做过研究。

Know, like I'm sure that people have written about this or done research.

但我发现，其实我们对这个了解得很少。

And I realized that it was very little was known.

就连胃肠病专家对此也知之甚少。

Even gastroenterologists knew very little about this.

第一份关于这些患者食物选择改变的临床报告，我记得是在2011年发表的。

The first clinical report that the alteration in food choices was common in these patients came out, I believe, in 2011.

后来，科学家们也在大鼠或小鼠身上重复了这项研究。

And then later on, scientists replicated that even in rats or in mice.

我们在实验室里也做过，结果一致，它们确实改变了食物偏好和选择。

We have done it in the laboratory and consistently they changed their food preferences, their food choices.

所以，近年来我们一直在研究这个系统。

So, in recent years we have been, we have been studying that system.

我要告诉你，在2022年，这是另一个重要的背景信息，我们还没有讲到那里。

And I will tell you that in 2022, this is another important contextual piece that we have not gotten to it.

所以，在我们发现并描述了这些细胞连接到神经系统，并且它们非常迅速地将信息传递到大脑之后，面临的挑战是：如果这是一种感觉，它影响的是哪种行为，对吧？

So, after we found and we described that these cells were connecting to the nervous system and that they were sending information up to the brain very rapidly, the challenge was, well, if this is a sense, what behavior is affecting, right?

它又是如何影响生物体的反应的呢？

How is it that is affecting the responses of the organism?

这需要克服一些技术上的障碍。

And that took a little bit of a technical hurdle.

而这时候就轮到光遗传学登场了。

And here is where optogenetics comes in.

好的，请给大家解释一下什么是光遗传学，至少从宏观层面讲一下。

Yeah, please explain for people what optogenetics is, at least at a top contour level.

好的。

Yeah.

光遗传学是在2005年，卡尔·迪塞罗教授以及其他科学家实现了这个实验梦想，他们分离出编码对特定波长光敏感的视蛋白的基因，并将它们植入神经元中。

So, optogenetics in 2005, Professor Carl Deisero, Irritable Bowel, and other scientists have been able to make this dream of an experiment, was isolate the genes that encode for these opsins that are sensitive to specific wavelengths of light and put them into neurons.

然后通过控制光照，他们就能让神经元被激活。

And now by turning that light, they could make the neuron activate.

后来呢，他们进一步发现，这项技术可以用来控制那些调节行为的特定细胞，从而确定哪些细胞在指挥某些行为，比如运动、进食、口渴、焦虑等等。

And then ultimately then, later on, they went on to describe that that could be used to control specific cells that are regulating behavior and then by that define what cells are orchestrating certain type of behaviors like movement, food intake, thirst, anxiety, so on and so forth.

所以2014年我们开始尝试把这项技术应用到肠道上。

So in 2014 we began trying to adapt that technology to the gut.

很快我们就发现，之前把光引入大脑的方式是通过一根硬质的光纤电缆。

And very quickly we realized that the way that was, that light was brought into the brain was through a fiber optic cable that was rigid.

在大脑里，硬质反而有帮助。

And in the brain, it helps that it's actually rigid.

但在肠道里就不行了，因为肠道一直在动，等等。

But in the gut, doesn't help because the gut is constantly moving and so on and so forth.

所以，用这种方式来做实验是行不通的。

So, it's not compatible for running those experiments.

这时候我通常会想，你看，我们真的不知道发生了什么，因为有些力量在我们周围移动。

And here's where I usually say, like, you know, we really don't know what is going on because some forces move around us.

然后在2017年，麻省理工学院的Paulina Nikkeva教授来杜克大学做了一场讲座。

And in 2017, Professor Paulina Nikkeva from MIT came to give a talk at Duke.

然后她主动联系了我。

And she reached out to me.

她真的来了，我们聊天的时候，她说，迭戈，我看你在研究肠道和大脑之间的这个交叉领域。

And literally, she came and as we were chatting, she said, Diego, I see that you're working between in this interface of the gut and the brain.

我这里有这种光纤，是柔性的。

And I have this fiber optic that is flexible.

你知道，这对你有没有用？

You know, would you have any use for it?

所以，有了这种光纤，对研究这些细胞如何控制行为起到了很大的作用。

So, with that fiber optic, that made a big difference to study interrogated function of these cells to behavior.

当我们能够把这些光敏蛋白，也就是光敏感蛋白，放进这些神经足细胞里，然后当我们打开光来快速关闭这些细胞时，我们发现了一些非常有趣的现象。

So, when we were able to put those opsins, the light sensitive proteins inside of these Neuropods, and now when we turn the light on to shut off these cells very rapidly, we found something very interesting.

通常情况下，当你给它们选择一种甜味剂，这种甜味剂没有热量。

So normally, when you give them the choice between a sweetener, which is devoid of caloric value.

就像阿斯巴甜、甜菊糖或者三氯蔗糖之类的？

So like a aspartame or spleen or stevia or something?

对。

Yeah.

是的。

Yep.

然后你给它们糖，普通的蔗糖，动物总是会去选择糖。

And you give them sugar, table sugar, the animal invariably will go to sugar.

它们更喜欢糖。

They prefer sugar.

它们更喜欢糖。

They prefer sugar.

如果它们以前没见过糖，可能需要多一点时间，但通常到第二天，它们能在九十秒内分辨出哪个是糖。

If they have never seen sugar, it will take them a little bit more time, but regularly, by the second day, is within ninety seconds that they detect what is sugar.

所以它们从一个管子里喝加了甜菊糖的水，从另一个管子里喝加了糖的水，它们总是更喜欢加糖的水。

So they're drinking out of one tube, they get some water with stevia, they drink out of another tube water with sugar, and they invariably prefer the water with sugar.

没错。

That's correct.

人们描述这个现象已经有一段时间了，事实上，在2007年，杜克大学的Ivan de Araujo教授做了一个很精巧的实验，实验中甜味受体，或者说味觉受体，被基因改造了。

And people have described this phenomenon for a while, in fact, in 2007, there was an elegant experiment done by Professor Ivan de Araujo at Duke University, in which the sweet taste receptors were, or the taste receptors were genetically raised.

这些动物无法区分甜味剂和水，但它们仍然能区分糖和水，这意味着还有其他东西在检测糖分。

And the animals were not capable of distinguishing the sweetener from the water, but they could still distinguish sugar from water, meaning that there was something else was So detecting that

为了让大家明白，这个实验是，在口腔层面消除甜味感知，并不会影响对糖水的偏好。

just to make sure people are on board, an experiment where sensing of sweet taste at the level of the mouth is eliminated, does not disrupt the preference for sugar water.

对。

Correct.

这意味着在意识层面之下，有某种机制让哺乳动物，包括我们人类，倾向于选择含糖的食物。

Which means that there's something going on below the depth of consciousness that causes mammals, and presumably us included, to prefer things that have sugar.

是的。

Yes.

然后，Tony S.

And then, Tony S.

Clafani，他一直在研究这些行为，他甚至提出，也许钠葡萄糖转运体是检测糖进入肠道的关键，正是这一点导致了这种偏好行为。

Clafani, he had been studying these behaviors and he went in so far to suggest that perhaps the sodium glucose transporters are some of the ones that are detecting the sugar as it enters the intestine and that's what is causing the behavior.

所以我们开始研究这个系统，我们想知道，是不是这些细胞在引导那种行为？

So we began working on the system and we wonder, could these cells be the ones that are guiding that behavior?

差不多在我们发表这项研究的时候，哥伦比亚大学的查尔斯·祖克教授也进一步推进了这个领域，他在之前研究的基础上，证明了脑干中有一群神经元在整合来自肠道的这些信息。

And around the time that we published this work, Professor Charles Zucker at Columbia also further advanced that area by building on the previous work and demonstrating that there were a population of neurons in the brainstem that were integrating this information from the gut.

这样一来，肠道和大脑就在共同引导这些行为。

And by that, the gut and the brain were guiding these these behaviors.

确实，从很小的时候起我们就渴望糖，或者至少，如果我们尝到糖的味道，就会倾向于想要更多糖。

And it is true that from the earliest of ages we crave sugar, or at least if we are exposed to the taste of sugar, it tends to drive seeking of more sugar.

你看，连婴儿都是这样。

I mean, you can see that in babies even.

对。

Correct.

而且我常说，我称之为本能，因为妈妈不需要教我们，嘿，迭戈，那是葡萄糖，你懂吧？

And as I usually say, I call it instinctively because our mother doesn't have to teach us, Hey, Diego, that is glucose, you know?

它可能以某种方式呈现给我们，但归根结底，我得去获取我的葡萄糖，获取我的氨基酸，对吧？

It may present us in some ways, but at the end of the day, I have to go and get my glucose, get my amino acids right.

因为吃东西其实很简单。

Because eating is very simple.

我们就是要想办法获取碳、氮、磷、钾、钠和氯，通过各种不同的方式和形式，对吧？

We're just trying to solve this issue of getting our carbons, getting our nitrogen, getting our phosphorus, our potassium, our sodium, and our chloride in so many different ways, shape or forms, right?

所以，我回到了那个实验，那个关键的实验。

So, I went back to the experiment, the key experiment.

当我们用光遗传技术，用光来快速关闭这些细胞时，当给动物提供甜味剂和糖的选择时，动物突然对这两种溶液失去了辨别能力。

So, when we were able to put these opsins and bring the light and shut off these cells very rapidly, When we had presented the animal with a choice of sweetener over sugar, then all of a sudden the animal became blind to the solutions.

它分不清甜叶菊，或者说甜味剂，和真正的糖。

It couldn't discern between the stevia, so to speak, or the sweetener, from the actual sugar.

而且整个操作，就是实验操作，是在肠道层面进行的。

And the entire manipulation, the experimental manipulation that is, is occurring at the level of the gut.

对，就是肠道。

The intestine, that's right.

就在胃后面，只是肠道的一小段。

Right after the stomach, it's like just a small portion of the intestine.

那么，如果我们尝试把这个应用到人类的真实生活体验中，如果我吃了一些冰淇淋，它尝起来是甜的。

So if we make an attempt to transfer this to the human real world experience, if I have some ice cream, it tastes sweet.

我喜欢它。

I like it.

现在我在想它，有点想吃。

And now I'm thinking about it and I'm craving it just a little bit.

我对甜食没有特别强烈的渴望，但我确实喜欢一些。

I don't have a huge craving for sweets, but I do like some of them.

所以吃冰淇淋，它尝起来是甜的。

So eating ice cream, it tastes sweet.

倾向于渴望更多。

The tendency is to crave more.

对。

That's correct.

对吧？

Right?

你得吃很多冰淇淋才能真正吃饱。

You have to eat a lot of ice cream before you're truly full.

对。

Yeah.

而且大多数人会自我控制，或者由父母来控制。

And most people self regulate or their parents regulate for them

对。

Yeah.

比如限制吃几勺之类的。

By limiting the number of scoops or something.

而那种甜味就是其中的一个动力。

And that sweet taste is part of the motivator.

但你说的是，当冰淇淋进入肠道时，那里有神经足细胞，它们也在感知糖分，并向大脑发送信号，大脑就会做出反应，去追求更多含糖的物质。

But what you're saying is that as the ice cream enters the gut, there are neuropod cells there that are also sensing the sugar and signaling to the brain and the brain is responding to pursue more of that sweet containing substance.

没错。

That's correct.

而且这一切都发生在我们意识不到的情况下。

And it's happening below our awareness.

这和冰淇淋的甜味是两回事。

It is independent from the sweet taste of the ice cream.

对。

Correct.

就是那种能意识到的甜味。

The conscious sweet taste.

能意识到的甜味。

The conscious sweet taste.

你想想看，其实我们并不是完全能意识到它的，对吧？

Which of you think about it, is not fully conscious, right?

你知道，我们能感知到的世界其实只是很小很小的一部分，对吧？

You know, as a, what we detect of the world is just a very tiny little portion, right?

就连视觉也一样，我们以为自己是在看光，但我根本不知道背后发生了什么。

Even sight, you know, like, we think we are looking for light, but I don't know what is happening behind my back.

我相信一切都很顺利。

I trust that everything is going okay.

当我们关闭这些细胞时，动物，就像我常说的，对糖变得视而不见了。

When we shut off these cells, the animal, and as I usually say, became blind to the sugars.

因为这有点像关闭了能够检测光线波长的细胞，而我们正是靠这些细胞来分辨颜色的。

Because it's kind of akin to having turn off the cells that are able to detect light, the wavelength of light, for us to be able to discern color.

对吧？

Right?

并不是动物失去了记忆，因为如果你把光移开，细胞又恢复功能了，动物又能区分一种溶液和另一种溶液了。

And it's not that the animal is losing its memory because then you remove the light and now the cells are functional again, then the animal again is able to distinguish one solution over the other.

然后我们又做了几个实验。

And then we did a couple more experiments in there.

如果我们反过来做会怎么样？

And what happens if we do the reverse?

如果我们现在打开这些细胞呢？

If we turn on the cells now?

有趣的是，当我们激活这些细胞时，老鼠会把甜味剂当作糖来吃。

And the fascinating thing is that when we turn on the cells, now the mouse will eat the sweetener as if it will be sugar.

有意思。

Interesting.

所以，激活这些细胞会让它们把无热量或低热量的甜味剂当作糖一样渴望。

So, the activation of these cells makes them crave non caloric sweetener or low calorie sweetener as if it were sugar.

但这是否让它们无法区分糖和低热量甜味剂呢？

But is it blinding them to the difference between sugar and low calorie sweetener?

这里还有另一个信息。

So here's another piece of information.

如果我们给它们提供水，并激活这些细胞，动物会像喝水一样喝糖水，会觉得很好喝。

If we will offer them water and we will turn on the cells, the animal will drink the water as if it will be sugar, like it will be appetizing.

即使那只是普通的水。

Even though it's just plain water.

是的。

Yes.

越来越明显的是，肠道在最基本的层面上就有这种感知能力。

What is becoming very obvious is that the gut has this sense at the most basic level.

这些感知系统实际上在计算几件事。

What the senses are doing is calculating a couple of things.

一个是刺激的显著性，也就是刺激有多强烈。

One is in the salience of the stimulus, is like how intense is the stimulus.

另一个是刺激的效价。

And the other one is the valence of the stimulus.

粗略来说，就是令人愉悦还是痛苦。

Is pleasurable or painful, so to speak, in like broad terms.

我这么说是因为在疼痛方面，David Julius教授、Holly Ingram教授和UCSF的Jim Byra做了很棒的研究，他们证明结肠中有一类释放血清素的细胞，他们特别关注结肠，这些细胞与脊髓的神经纤维相连。

And I say this because on pain side, Professor David Julius, Professor Holly Ingram, Jim Byra at UCSF, they have done some beautiful work demonstrating that there are these serotonin releasing cells, specifically in the colon, they have focus in the colon, that they couple to nerve fibers of the spinal cord.

当这些细胞被激活时，突然就会引发我们临床上所说的内脏高敏感性。

And when they are activated, now all of a sudden they drive what we call in the clinical realm visceral hypersensitivity.

所以它们负责触发神经纤维（结肠神经纤维）的高敏感性，因为它们能检测到有害刺激，然后最终将这些有害刺激传递到神经纤维上，粗略地说，就是作为疼痛信号传递过去。

So they are responsible for triggering the hypersensitivity of the nerve fibers, the colonic nerve fibers, because they detect noxious stimuli and then ultimately they gate that noxious stimuli and pass it on to the nerve fiber as, in broad terms, as a painful stimulus.

所以这就是肠易激综合征吗？

So is this irritable bowel syndrome?

是的，我们可以把它看作是可能发展成肠易激综合征等疾病的生物学基础，或者临床上称之为慢性胃肠疾病，也就是所谓的肠脑互动障碍。

It is, we could call it as the biological basis of what could degenerate into irritable bowel syndrome and so on and so forth, or these chronicle GI, they call them disorders of gut brain interactions in the clinic.

我想稍微休息一下，感谢我们的赞助商InsideTracker。

I'd like to take a brief break and acknowledge our sponsor, InsideTracker.

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InsideTracker is a personalized nutrition platform that analyzes data from your blood and DNA to help you better meet your personal health goals.

我一直坚信定期做血液检查，因为很多影响你短期和长期健康的因素，只有通过高质量的血液检测才能分析出来。

Now, I've long been a believer in getting regular blood work done for the simple reason that many of the factors that impact your immediate and long term health can only be analyzed with a quality blood test.

现在，市面上很多血液检测的问题是，你得到了关于代谢指标、血脂、激素等方面的信息，但不知道该怎么处理这些信息。

Now, the problem with a lot of blood tests out there is that you get information back about metabolic factors, lipids, and hormones, and so forth, but you don't know what to do with that information.

而InsideTracker提供了一个非常易于使用的在线平台，让你能看到血液检测结果，并提供各种可操作的工具，比如行为、营养和补充剂方面的建议，帮助你把这些指标调整到最适合你的范围。

With InsideTracker, they have a very easy to use online platform that allows you to see the results of your blood test and then offers you various actionable tools, such as behavioral tools, nutritional tools, and supplementation tools that can help you move those values from your tests into the ranges that are optimal for you.

如果你想尝试InsideTracker，可以访问insidetracker.com/huberman，享受他们新订阅模式10%的折扣，这个模式的价格已经大幅降低了。

If you'd like to try InsideTracker, you can go to insidetracker.com/huberman to get 10% off their new subscription model, which has significantly reduced prices.

再说一遍，访问 insidetracker.com/huberman 就能享受九折优惠。

Again, that's insidetracker.com/huberman to get 10% off.

作为一名神经科学家，我受过的训练让我想到的是神经视网膜，也就是眼睛后部的感光组织，还有耳蜗，也就是内耳里那些对声波做出反应的机械感觉细胞，它们不是直接反应，而是通过一系列不同的换能器之类的机制。

As a neuroscientist, I was trained to think about the neural retina, the light sensing tissue at the back of the eye, the cochlea, the essentially mechanosensory cells in the inner ear that respond to sound waves, not directly, but through a number of different transducers and this kind of thing.

当然，你们也都熟悉皮肤，它对压力、轻触、痒、刺痛等等都有反应。

And then of course, where you are all familiar with the skin and that it responds to pressure, light touch, tickle, itch, etcetera.

根据你告诉我的，我现在理解的是，从口腔到直肠的整个通道上，我们都有感觉细胞在评估我们所吃食物的化学成分。

What I'm understanding based on what you're telling me is that all along the pathway from our mouth to our rectum, we have sensory cells that are evaluating the chemical constituents of the foods that we eat.

它们会释放出那种宽泛的、甚至可以说是粗略的缓慢信号，以激素的形式来改变我们的食欲、我们的幸福感，也许还有我们的不适感，但同时也会向大脑发送直接信号，驱动某些类型的思维、情绪和行为。

Emitting broad kind of maybe even crude slow signals in the form of hormones to change our appetite, our feelings of well-being, maybe our feelings of not well-being, but also sending direct signals to the brain to drive certain types of thinking, emotions, and behavior.

通过这条从肠道出发的通路，食物已知会引发哪些类型的思维、情绪和行为呢？

What sorts of thoughts, emotions, and behaviors are foods known to evoke through this pathway from the gut?

因为你那个朋友的故事，做了胃绕道手术之后，对单面煎蛋的渴望或者厌恶完全改变了，这说明这个系统一开始就像我说的那样相当粗糙，但最终却汇聚到非常精细的决策上，你点这个，避开那个。

Because the story about the your friend that had the gastric bypass and then changed the relationship completely to the craving of or the aversion to sunny side up eggs indicates that it's a pretty crude as I'm describing a system to begin with, but it ultimately converges on pretty fine scale decision making, you order this and you avoid that.

你真的很喜欢这个，而对另一个东西光是想到就几乎要恶心了。

You really like this and you really are almost nauseous at the thought of something else.

这可是很高层次的决策。

That's pretty high level decisions.

可能对大多数人来说不觉得，但它确实在显著影响行为，或者说在很高的层面上影响行为。

It might not seem like it to most, but it's impacting significant behavior or impacting behavior at a significant level.

没错。

That's correct.

说到那个具体例子，我觉得是肠道重新连接之后，肠道变得对刺激非常敏感。

And when I think about that specific example is that after there has been this rewiring of the intestine, Then, now the intestine is very sensitive, so to speak, to the stimuli.

当蛋黄里的脂质开始进入肠道时，如果这种敏感性发生了变化——可能是对刺激的反应速度变了，或者传递信号的速度变了，或者对刺激的显著性或强度的敏感度变了——它可能会传递出这样的信号：以前一点点量就会让人反感。

And when those lipids from the yolk start to enter the intestine, if that sensitivity has changed, meaning it could have changed in how fast it reacts to the stimulus, or how fast it communicates to the stimulus, and how sensitive it is to the saliency or the strength of the stimulus, it could communicate that, oh, what it used to be repulsive with a tiny little bit amount.

现在，一点点量反而让人愉悦。

Now, it is actually pleasurable with a tiny little bit of amount.

这里有个很清楚的例子。

And here's a clear example.

所以，临床上已经有很多记录，做胃分流手术的患者，实际上更容易出现这种情况。

So, it has been very well, I will say that it has been documented in the clinic that patients that undergone gastric bypass surgery, they're actually more prone.

我觉得大概有两到七倍吧。

I think that it goes from like two to seven fold.

他们患上酒精依赖的可能性。

The likelihood that they become, they will develop alcoholism.

真的吗？

Really?

是的。

Yes.

因为现在，他们描述的情况是，比如，以前我不喜欢红酒，但手术后几个月，我喝一杯红酒，然后突然发现自己喝了两杯、三杯、四杯，然后他们要么变得更敏感。

Because now, the way that they describe it is like, well, know, either before I didn't like wine, and then now, after a few months of a surgery, I'll have one glass of wine, and then all of a sudden I found myself going to two, three, four, and then they will become either more sensitive.

虽然整个生物学机制还不完全清楚，但他们不仅变得更敏感，而且对这种刺激更感兴趣。

It's still not known the entire biology, but they will become either, not only more sensitive, but more attracted to that type of stimulus.

我忍不住想问关于奥泽匹克、蒙加罗和GLP-1，也就是胰高血糖素样肽-1类似物，这些现在真的很火，至少讨论起来是这样，因为现在有成千上万的人在用这些药治疗糖尿病和减肥。

I can't help but ask about Ozempic, Mounjaro, and GLP-one, glucagon like peptide one analogs, which are really kind of all the rage right now, at least for discussion about many, many, many millions of people are now taking this for treatment of diabetes and for weight loss.

据我了解，GLP-1作用于大脑的下丘脑来减少饥饿感，同时也作用于肠道，产生更明显的胃胀感。

My understanding is that GLP-one acts at the level of the brain, the hypothalamus to reduce hunger, but also at the level of the gut to give the sensation of more gastric distension.

有没有研究知道GLP-1是否与神经足细胞以及你描述的这个通路有相互作用，考虑到这些神经足细胞在渴望或厌恶中的作用？

Is there any knowledge of whether or not GLP-one interacts with the neuropod cells and this pathway that you're describing, given what these neuropod cells do for craving or aversion?

是的，这是个很好的补充问题。

Yes, that's a complimentary question.

事实上，当我十五年前开始研究这个领域时，这个领域的科学家们就已经对胰高血糖素样肽非常感兴趣了。

And in fact, when I got into studying in this field fifteen years ago, the study among scientists in this area, glucagon like peptide was already very popular in this study.

实际上，在这个领域，人们非常专注于研究这种肽。

In fact, in this area, people were very focused on the study of this peptide.

他们之所以这么专注，是因为它是胰腺中刺激胰岛素释放最有效的物质之一。

And they were very focused on the study of this peptide because it was one of the most potent stimulators of insulin release in the pancreas.

在胃旁路手术后，它的循环水平实际上会增加。

After gastric bypass surgery, it will actually increase its amount in circulating levels.

而且已经有一些研究表明，这种胰高血糖素样肽的作用实际上不是通过血液循环，而是更局部地作用于神经纤维，尤其是迷走神经。

And there were already some studies suggesting that the effect of this glucagon like peptide, it was actually not through the circulation, but more in a localized action onto nerve fibers, especially of the vagus nerve.

所以，当时已经有一些关于这个的讨论在进行中。

So, there was already some ongoing discussion about this.

当然，这些肠内分泌细胞，也就是神经内分泌细胞，至少在动物身上，主要分布在消化道更靠后的位置，它们确实会释放这种胰高血糖素样肽。

And certainly, of these enteroendocrine cells, these neuroendocrine cells, particularly at least in animals, think is more distal and in the digestive tract, that they do release this glucagon like peptide.

首先，主要是响应所有宏量营养素，但主要是糖分。

One, in response to primarily all of the macronutrients, but primarily sugar.

然后，这些胰高血糖素样肽-1会作用于神经末梢上的特定受体，从而触发一些行为。

And then, these glucagon like peptide one will act on specific receptors of the nerve terminals and then will trigger some of the behaviors.

人们也认为它作用于脑干层面。

It's also thought that it acts at the level of the brainstem.

它增强的效果是降低食欲。

And what it will potentiate is the reduction of appetite.

所以我说这是个补充性的问题，因为最初几毫秒发生的是实际的选择和对食物的实际感受。

So, I say that this is a complementary question because what is happening in the first few milliseconds is the actual choice and the actual feeling of how you feel about food.

而几分钟到几小时后发生的是食量。

And what is happening in the minutes to hours later is the amount.

你能吃多少，对吧？

How much you can eat, right?

以及你什么时候应该停下来。

And when you should stop.

因为四个小时后，你会再次感到肠胃的蠕动，因为肠道又开始搅动，开始呼唤食物。

Because after four hours you're going to come back and feel again the tickling of the gut because the gut starts to churn again and it starts to call for food.

记住，它要养活两个巨大的生物体，一个是宿主本身，另一个是体内的微生物，对吧？

Remember, it has to feed two giant organisms, the host itself, but also the microbes that are inside, right?

所以，它必须每隔四个小时左右维持饥饿感，对吧？

So, it has to keep, so to speak, hunger going every four hours or so, right?

所以，这就是为什么激素更多是按照昼夜节律周期性地起作用，而神经递质则是在胃肠道特定区域对精确刺激做出非常快速的反应。

So, that's why the hormones are more acting on the cyclical circadian way, but the transmitters are acting in this very fast, responsive way of the precise stimuli in specific regions of the gastrointestinal tract.

那么，这些神经内分泌细胞是释放GLP-1，还是对GLP-1做出反应？

So, these neuroendocrine cells are releasing GLP-one, or responding to GLP-one?

它们释放GLP-1。

They are releasing GLP-one.

它们释放GLP-1来暂时抑制饥饿感。

They're releasing GLP-one to shut down, transiently shut down, hunger.

而且这些细胞之间可能也有相互作用，你知道，专业术语叫自分泌，或者它们之间还有旁分泌，也就是神经调节。

And probably there is some interaction between these cells that they are having, you know, the technical term is autocrine, or they are having like paracrine between the cells, you know, neuromodulation.

但主要来说，它们是对刺激做出反应，然后把GLP-1释放到神经纤维上。

But primarily, let's say, they respond to the stimulus and release GLP-one onto the nerve fiber.

我

I

我有一个理论，虽然没有直接的数据支持，但我想听听你的想法。我之前和很多研究营养的人聊过，也在之前的节目里讨论过肠道-大脑连接和微生物组，其中一个关键点是，人类在某种程度上无意识地，但也是有意识地学习到，某种食物和它的宏量营养素含量、碳水化合物、蛋白质和脂肪的比例、味道、热量以及物理体积，还有微量营养素之间的关系。

have a theory for which I have no direct data, but I'd like your thoughts on having spoken to a lot of people that work on nutrition, but also gut brain access today and microbiome in previous episodes, that one of the key things that a human learns somewhat unconsciously, but also consciously is the relationship between a given food, which macronutrients it contains, the ratios of carbohydrate, protein and fat, the taste of that food, the amount of that food translated into calories, but also physical volume, and then the micronutrients.

我为什么这么说呢？

Why do I say this?

嗯，有越来越多的研究表明，摄入高度加工的食物会导致摄入过多的热量，或者比吃更天然的食物摄入更多的热量。

Well, there are a growing number of studies showing that the ingestion of highly processed food leads to the intake of excess calories or more calories than if one consumes foods in their more natural form.

单一成分或两种成分的食物，和含有多种成分的食物是很不一样的。

Single ingredient foods or two ingredient foods are very different than a food that has a bunch of different things in it.

在我看来，如果我们回顾一下人类的进化史，当然，人们很久以前就开始炖汤、煮粥之类的了。

And it seems to me that if we were to look back into our evolution, sure, people were making stews and soups and things for a long time.

三明治的出现大概是因为图方便或者好吃，或者两者都有，就是把肉和蛋白质夹在两片面包之间，差不多就是这样。

Presumably the sandwich came about through either desire for convenience or taste or both, putting meats protein in between two pieces of bread, something of that sort.

按照三明治的定义，里面可能还会加些蔬菜、奶酪，但整个肠道这条通路要做的，似乎就是分解吃进来的东西，分析这里有什么，然后影响你的食物选择，就像你提到的，包括决定吃多少、要不要再吃这种食物，或者避开它。

By definition of a sandwich, maybe some vegetables in there as well, some cheese, but that what this whole pathway along the gut is trying to do it seems is to deconstruct what's coming in, what's here and shaping choices as you mentioned about food choice, including the amount of food to further consume and whether or not to return to that food or to avoid it.

在极端情况下，这看起来很简单明了。

At the extremes, it seems pretty straightforward.

这是一个非常经典的案例，对吧？

And this is a very classically described case, right?

你去某个地方吃了宫保虾仁，或者喝了扁豆汤，几个小时后感觉不对劲，开始出汗、胃不舒服，然后你对那种食物产生强烈的厌恶，甚至可能对整顿饭、那家餐厅，甚至那种菜系都反感，这取决于你是喜欢归类还是细分，就像我们科学界说的，对吧？

You go and you have the Kung Pao shrimp, or you have the lentil soup at a given place and a few hours later, don't feel right, start some sweating, some gastric distress, and you develop a pretty broad aversion to that food or maybe even the entire meal, maybe the restaurant, maybe even that entire type of cuisine, depending on how much of a lumper versus a splitter you are, as we say in science, right?

你是做大的分类决定，还是做细的分类决定。

How much you make kind of large bin decisions or fine bin decisions.

用大白话说就是，你是回到同一家餐厅点别的菜，还是决定再也不去了。

This is nerd speak for saying, do you go back to the same restaurant but order something different or do you just decide to never go back again?

但那是比较极端的情况，对吧？

But that's a pretty extreme case, right?

另一个极端是，你吃了一种食物，觉得特别好吃，感觉特别好，餐厅、人也都很好，然后你就特别想吃更多这种食物。

The other extreme would be you eat a food, it's delicious, you feel wonderful, the restaurant, the people it's wonderful and you crave more of that food.

对吧？

Okay?

还有各种环境因素呢。

There's all the contextual stuff too.

但我们真正在讨论的是，人们如何在这个关于吃什么、怎么吃、营养如何影响我们的一切——从当下的感受、味道，到我们是否认为它对我们有益，再到我们是否觉得它影响了我们的身体成分和健康——这个复杂的领域里做出选择。

But what we really are talking about here is how one navigates this whole landscape of what to put into one's body in terms of nutrition and trying to understand how that's impacting everything from how we feel right away, how it tastes, whether or not we conceive it as good or bad for us, whether or not we think it's impacting our body composition and health in ways that we want or don't want.

这确实很复杂，对吧？

I mean, it's pretty complex stuff, right?

这至少跟去大都会艺术博物馆看一幅画，然后试图判断自己是否真的喜欢那幅画一样复杂。

This is at least as complex as going to Metropolitan Museum of Art and looking at a painting and trying to evaluate whether or not you really like that painting or not.

实际上，可能比那还要复杂得多。

In fact, it's probably much more complicated than that.

但这就是我们每天都在做的事。

But it's what we do.

我开始又有一种感觉，不是双关语，就是这条我们称之为“肠脑轴”的通路，真的是一种非常复杂的第六感。

And I'm beginning to get the sense again, no pun intended that this pathway that we call the gut brain axis is really, it's a sixth sense of a very elaborate kind.

你刚才提到了一个我特别喜欢的领域，因为作为科学家，我们有时候会周游世界。

So you just touched on an entire realm of a topic, which is one of my favorite topics, because at some point, you know, we as scientists, we travel the world.

我渐渐发现，不管我去哪里，大家解决食物问题的方式都差不多。

And it started to become very obvious to me that wherever I went, we solve this issue of food in a very similar way.

不管是玉米饼还是两片面包，其实都是碳水。

Whether it's a tortilla or two pieces of bread, which is another way of a tortilla, you have your carbs.

然后加点肉或者蘑菇，就有了蛋白质。

And then you add a little bit of meat or a mushroom, and now you have your protein.

或者鱼或者鸡肉。

Or fish or chicken.

或者鱼或者……

Or fish or The

肉食主义者会说蘑菇不算蛋白质，而素食主义者会说蘑菇、豆子、扁豆都是很好的蛋白质。

carnivores will say mushrooms, not a protein, the vegans will say mushroom, beans, lentils, great protein.

我们不是来争论这个问题的。

We're not here to resolve that debate.

你按自己的选择来就好。

Do as you choose.

然后再加上生菜或者蔬菜。

And then you add the lettuce or the vegetables.

这里就是讨论的第一个关键点，因为这一点非常有意思。

And here's the first stop in that discussion because this is fascinating.

最近有一些研究表明，如果你从饮食中去掉蛋白质，动物吃下那顿饭，肠道会检测到里面没有蛋白质，然后它就会停止吃那顿饭。

There are some recent work showing that if you remove the protein from a diet, the animal swallows that meal, the gut evaluates that there is no protein in there, and it stops eating that meal.

哇，这就像点了素墨西哥卷。

Wow, so this is like ordering the vegetarian taco.

对。

Yeah.

或者墨西哥卷饼或三明治，之后就会避开那个特定的卷饼或三明治，因为它缺少蛋白质。

Or burrito or sandwich, and then avoiding that particular taco or sandwich thereafter, because it lacks protein.

因为它缺乏蛋白质。

Because it lacks protein.

好的。

Okay.

所以，以后就会避开那些缺乏动物蛋白的食物。

So, foods that lack animal based proteins tend to be avoided going forward.

那么，这是第二点。

So, here's the second part of that.

实际上，如果蛋白质含量低，而不是完全没有。

In fact, if the protein is low, not completely absent.

如果蛋白质含量低，动物会吃更多这种食物，因为它试图弥补蛋白质的不足。

If the protein is low, the animal consumes more of the diet because it's trying to compensate for the lack of protein.

而且显然，如果这种食物含有更令人愉悦的糖分或脂肪，它就会一直吃，对吧？

And obviously, if it has sugars or fats that are more pleasurable, it keeps eating that meal, right?

明白了。

I see.

如果蛋白质完全缺失，动物就会避开这种饮食。

If the protein is completely absent, the animal avoids that diet.

除非这种饮食富含膳食纤维。

Unless that diet is very rich in dietary fibers.

我看到的一项研究让我觉得特别有意思，就是消化道里的微生物，如果它们有足够的高消化性纤维，它们就会开启合成必需氨基酸的能力。

And the study that I saw, which I thought was fascinating, is that because somehow the microorganisms in the digestive tract, if they have enough highly digestible fiber, now they turn on the ability to synthesize essential amino acids.

真的吗？

Really?

是的。

Yes.

所以，我们的肠道，也就是肠道里的神经元，其实一直在等着，盼着，我们能给它们提供来自动物来源的蛋白质。

So, our gut, meaning the neurons in our gut are essentially waiting for, hoping, we'll give them a consciousness, proteins from animal sources.

没错。

That's correct.

如果这些动物蛋白以肉、鱼、蛋等形式到达，细胞就会向大脑发出信号，让我们渴望更多这些食物，直到饱腹为止。

If those animal proteins arrive in the form of meat, fish, eggs, etcetera, the cells signal to the brain craving more of those foods until satiety is reached.

但是如果没有那种蛋白质，动物很快就会学会，人也会很快学会避开那种特定的食物，除非里面有纤维，在这种情况下，这些肠道细胞就能合成必需氨基酸了。

But in the absence of that protein, the animal quickly learns, the person quickly learns to avoid that particular food, unless there's fiber in it, in which case these gut cells are able to now synthesize the essential amino acids.

是微生物。

The microorganisms.

抱歉，是肠道微生物，我们现在说的是肠道菌群，它们能合成那些通常来自肉类、鸡肉、鱼类或其他的必需氨基酸。

Excuse me, the microorganisms of the gut, here we're talking about the microbiome now, can synthesize the essential that amino ordinarily would come from the meat, chicken, fish or

没错。

That's right.

哇，那真是太神奇了。

So wow.

所以我是个杂食动物。

So I'm an omnivore.

我喜欢吃肉，高质量的肉，但我也喜欢蔬菜、水果和某些种类的淀粉。

I love meat, high quality meat, but I also love vegetables, fruits and starches of certain kinds.

但我有些朋友是素食者或纯素食者。

But I have friends who are vegetarian vegan.

他们很多人吃素，饮食里有很多纤维，而你是说纤维本身就能促使肠道微生物组合成那些通常来自肉类的必需氨基酸。

Many of them eat a vegetarian vegan diet that includes a lot of fiber and you're saying that the fiber itself can trigger the gut microbiome to synthesize the essential amino acids that ordinarily would come from meat.

但你还说过，如果我没记错的话，如果食物里有一点蛋白质，不是零蛋白质，而是少量蛋白质，那我们就会更想吃那种食物，试图去……

But you also said, if I recall that if there's a small amount of protein, so not zero protein, but a small amount of protein in there, then we crave more of that food in order to try and

补充。

get Compensate.

蛋白质。

Protein.

非常有意思，因为这对我来说，第一次把两种观点统一起来了：一种观点是基于观察或假设，认为我们本质上是在寻找氨基酸的机器，而完整的蛋白质，比如肉、鱼、鸡、蛋等等。

Very interesting, because this is the first thing that to me squares the argument based on the observation that, or the hypothesis that we are essentially amino acid foraging machines and that complete proteins in the form of meat, fish, chicken, eggs, etcetera.

你知道，有人会说那些是最好的蛋白质形式，对吧？

You know, there are those that argue those are the best forms of protein, right?

最完整的蛋白质，但也有很多素食者和纯素食者，他们靠素食和纯素饮食也能活得很好。

The most complete forms, but there are many vegetarians and vegans who seem to thrive on a vegetarian vegan diet.

而你现在告诉我，也许他们的身体，他们的肠道微生物组，正在弥补缺乏完整动物蛋白的不足。

And you're telling me that perhaps their body is, their gut microbiome is compensating for the lack of whole animal protein.

没错，那些试图限制肉类摄入的人，总体上是不是更饿？

That's right, and the the people who are trying to limit their meat intake are what, hungrier in general?

所以你要么就尽情吃，要么就完全不吃，而不是只吃一点点。

So you're better off either indulging it or avoiding it, but not having a small amount of it.

是这个意思吗？

Is that the idea?

意思是身体或肠道能够察觉到这一点，然后会试图补偿，对吧？

The idea is that the body or the gut will be able to detect that and then will try to compensate, right?

明白了。

I see.

这个，我最近其实是从一个朋友那里学到的，她叫劳拉·杜瓦尔，在哥伦比亚大学工作，她做了一些关于蚊子以及它们如何吸血的漂亮研究。

And this, I actually learned recently from a friend, Laura Duval, at Columbia, who works, does some beautiful work on mosquitoes and how it is that they feed on blood.

她来参加了“美食宇航员”系列节目。

She came for the Gastronauts series.

她是莱斯利·瓦尔萨尔那边的人吗？

Is she from Leslie Valsal?

对。

Yeah.

瓦尔萨尔。

Valsal.

对。

Yeah.

我了解到的是，当蚊子不繁殖的时候，它们可以不用ATP，也就是能量分子，对吧？

What I learned is that when the mosquitoes are not reproducing, they can leave off ATP, which is the energy molecule, right?

但是，它们不能产卵。

But, they cannot lay eggs.

它们需要蛋白质才能产卵。

They need the protein in order to be able to lay eggs.

否则，蚊子就无法产卵，你知道的。

Otherwise, the mosquitoes cannot lay the egg, you know.

所以这让我们看到，肠道感应细胞，也就是这些神经足细胞，对食物中的氨基酸含量非常敏感，这完全说得通。

So this leaves us with a picture of the gut sensing cells, these Neuropod cells as exquisitely sensitive to amino acid content in our foods, which makes perfect sense

而且这个还没有发表或展示过。

to And it has not been published or demonstrated yet.

当然。

Sure.

我们现在已经进入新数据领域了。

We're now in the realm of new incoming data.

在量子力学中，是的。

In QM, yeah.

我们想强调这一点，把它括起来，加粗并下划线，因为我们现在正处在可能到来的前沿。

We wanna highlight this, bracket it, boldface and underline it as we're now at the cutting edge of what may be coming.

没错。

That's right.

观察。

Observation.

但尽管如此，还是很有趣。

But nonetheless, very interesting.

但是有一个由来已久的假说，说我们之所以渴望必需氨基酸，是因为它们是大脑和身体里很多重要东西的构建基础。

But there is this fairly long standing hypothesis that we are forging for essential amino acids because they are the building blocks of so many important things in the brain and body.

而且事实上，确实有证据支持这一点。

And in fact, there is evidence on that.

澳大利亚悉尼大学营养研究所的史蒂文·辛普森教授，就是蛋白质杠杆假说的主要倡导者。

And Professor Steven Simpson in Australia, in the Nutrition Research Institute at Sydney University, he is a main proponent of this protein leverage hypothesis.

实际上，蛋白质是最能让人满足的宏量营养素。

And in fact, protein is the most asserting macronutrient.

这一点已经得到了证实。

So, that has been established.

所以，我们通常关注糖和脂肪，但有点忽视了蛋白质，因为它不像糖和脂肪那样让人愉悦。

And that's why normally we have focused on sugars and fats, but we have neglected a little bit on the protein because it's not as pleasurable as the sugars or fats.

但有趣的是，它却是最能让人有饱腹感的营养素。

But what is fascinating is that it is the most satiating nutrient.

而且你也知道，它就像是最稀缺的，甚至从商业角度来说，也是最贵的，对吧？

And as you know, it's like the most limiting and also like, even commercially, it's the most expensive, right?

是的，我确实有过这样的经历，在我人生的某个阶段，我非常喜欢甚至渴望甜食、甜点、糖之类的东西。我注意到，随着时间推移，如果我吃足够的肉、鸡肉、鸡蛋、鱼——当然不是说吃太多——我对糖的渴望就会大大降低。

Yeah, I certainly have had the experience of, at one time in my life, really enjoying and even craving sweet foods, desserts and sugars and things of that sort, and I noticed that over time, if I eat sufficient amounts of meat, chicken, eggs, fish, which is not to say that I consume excess amounts of them, that my sugar cravings go way, way down.

这只是我个人的经历，但我知道我的家人和其他人也有类似的感受。

That's just my personal experience, but I know it's an experience that family members of mine and others share as well.

但我向你保证，这个话题很有趣，对吧？

But I promise you that this was a fun topic, right?

我们不能只停留在第一层。

We couldn't stop at like just layer number one.

第二层是，在农业中，我们有种植的本能。

Layer number two is that in agriculture, we have this instinct to plant.

种植互补的植物。

Plants that complement each other.

比如，一个经典的例子，尤其是在原住民社区中，叫做“三姐妹”。

Like for instance, a classic, especially among native communities is called like the Three Marys.

我相信是南瓜，或者某种纤维作物，加上玉米（碳水化合物）和豆类。

I believe it's pumpkins, or some type of fibers with corn, carbohydrates, and beans.

所以在纯植物饮食中，人们会努力获取纤维、糖分和氨基酸。

So in purely plant based diets, there's an effort to get the fiber, the sugar, and the amino acids.

没错。

That's right.

我在农场长大，我父母有农场，我记得他们种地的时候，也会把豆子种进去，豆子会绕着玉米生长。

And I grew up in a farm, my parents got farms, and I remember when they would plant, they would also throw in there the beans, and the beans will wrap around the corn.

这看起来非常自然，你也会这么做，因为你就是这么学的。

And it just seemed like so natural and that's what you will do because that's what you learn to do.

但仔细想想，这是我们在农业上发展出来的一种本能，可能是在潜意识里，我们会这样种植，或者也许是植物教会了我们这样种植，以至于现在我们把它们放在盘子里时，从营养角度来说，一切都说得通。

But if you think about it, it's an instinct that we have developed even agriculturally, probably in the subconscious, to cultivate them in such a way, or perhaps the plants taught us how to cultivate them in such a way that now when we put them in the plate, it just makes sense at the nutritional level.

因为你想，每次我们吃饭的时候，我们是怎么摆盘的呢？

Because if you think about it, every time that we go to eat, how is it that we arrange that plate, right?

米饭缺乏一些必需氨基酸，但富含碳水化合物，对吧？

There is some rice which is very deficient in some essential amino acids, but is rich in carbohydrates, right?

还有豆子，对吧？

It has some beans, right?

然后还有一些生菜，你知道吗？

And then there's some lettuce, you know?

有时候，对于杂食者来说，人们会放肉或者其他的蛋白质进去，对吧？

And sometimes it would have like for omnipores, people would put meat or you would put other types of protein in there, right?

当然，这也会因文化、季节、食物供应等因素而有所不同。

And certainly it varies by culture, time of year, food availability, and things of that sort.

既然我们聊到了你的成长经历，你的故事真的很吸引人。

As long as we're talking about your upbringing, you have a fascinating story.

也许我们可以花几分钟聊聊这个。

So maybe we could discuss that for a few minutes.

你出生在哪里？

Where were you born?

我出生在厄瓜多尔的亚马逊地区，一个叫埃尔查科的小镇。

I was born in the Amazonia of Ecuador, a small town called El Chaco in Ecuador.

它位于安第斯山脉东坡，通往亚马逊地区的路上，在纳波省。

It's on the slopes of the Eastern slopes of the Andes on the way to the Amazonia in the Napa Province.

巧合的是，当年弗朗西斯科·德·奥雷利亚纳在1542年行军发现亚马逊河的路线，正好经过我们那里。

Coincidentally, it was like through the path from where Francisco de Orellana in 1542 marched on its way to the discovery of the Amazon.

那条路实际上穿过一条小径，后来我读到资料才知道，原住民在亚马逊、安第斯山脉和沿海地区之间，已经用这些小路走了几千年了。

It actually passed through a trail that later on reading, I realized that native people had all of these trails between the Amazonia and the Andes and the coastal line for thousands of years.

你是在一个非常偏远的乡村长大的——

You grew up in a very rural

是的。

Yes.

早在二十世纪二十年代，厄瓜多尔就发现了石油。

Oil had been detected in the nineteen twenty's in Ecuador.

1964年进行了第一次勘探，第一口油井在一个叫拉瓜格里奥的小镇，那里离我长大的地方现在只要三四个小时的车程。

It was first explored in 1964 in the first oil well was in a town called La Guagrio, which now is only like three or four hours from the town where I grew up.

但那时候要八个小时，路况很差。

But at that time, it was like eight hours, the roads were not good.

1974年，第一条公路才修到伊达。

And the first road passed through Hida in 1974.

我1983年出生，但我记得我们以前有个巨大的柴油发电机，只有晚上七点到九点供电照明。

I was born in 1983, but I remember that we used to have like a giant diesel engine that will give us light electricity only from seven to nine pm.

记得我爸爸买了镇上第一台彩色电视机，然后邻居们都会来我们家客厅一起看电影。

Remember when my father bought the first color television in the town, and then neighbors would come to our living room and then we would watch movies.

哇。

Wow.

那是八十年代的事。

This was in the eighties.

对，就是八十年代。

That was in the eighties, right?

这样的成长经历真有意思。

Such an interesting upbringing.

那你当时是纯吃素，还是也吃肉？

So did you eat a purely vegetarian diet or you ate meats as well?

如果吃肉的话，那些肉是从哪里来的？

Where did those meats come from if you did?

主要是牛、山羊和绵羊。

Primarily from cattle, goats, sheep.

那你是怎么从亚马逊地区转到研究营养学，最后又研究神经科学的呢？

So how do you go from the Amazon to a study of nutrition and ultimately neuroscience?

对。

Yeah.

这正是问题所在，对吧？

That's the question, right?

我越深入，就越怀疑这一点。

Like, the deeper I go, the more I question this.

我以前觉得这很简单，你知道，特别是当我11岁的时候，我父亲，他出生于1932年。

I used to think that, oh, it was very simple, you know, like when I was, specifically when I was 11 years old, my father, he was born in 1932.

他19岁时失去了父亲，也就是我的祖父，那时他才六岁。

By 19, he lost his father, my grandfather, when he was six years old.

他被送走了，不得不自己去闯荡生活。

And he was given away and he had to go and like build his life.

他是一位非常成功的企业家。

He was a very successful entrepreneur.

但在这个过程中，他结交了很多朋友和熟人。

But in the process, he had made a lot of friends and acquaintances.

所以，我11岁那年，我记得很清楚，他一个在特种部队的朋友路过我们家，因为那是我们进入亚马逊丛林的主要道路，军队和特种部队的人都会走那条路。他停下来，说：“嘿，罗赫略。”

So, I was 11 years old, I remember specifically that a friend of his who was in the Special Forces stopped by our home because that was the main road that we go into the Amazon Jungle where the folks in the special forces in military will And be he stopped by and said like, Hey, Rogelio.

“你打算拿迭戈怎么办？”

What are you gonna do with Diego?

“我觉得是时候了，你应该送他去军校。”

I think that it is about time that I think that you should send him to the military school.

我记得就在短短两三周内，我参加了考试，被军校录取了，然后我就进了军校。

And I remember in a matter of like, literally a couple of weeks or three weeks, I had taken the tests and I was accepted into the military school and then I ended up in a military school.

那时候，那是全国最顶尖的军校。

And this was the, at that time, was the premier military school in the country.

光是这一点，随着年岁的增长，你才开始理解自己成长的环境。

That alone, it was, with years you started to understand the context in which you developed.

因为对一个孩子来说，那是一个非常有意思的环境。

Because it was a very interesting context for a child.

举个例子，这所学校有全国第一个也是唯一一个动物园。

Like, just to give you an idea, this school had the first and the only zoo in the country.

所以，我在教室里就能直接看到狮子。

So, from my classroom, I would literally look at the lions.

然后，大概是我在学校的第二年或第三年，因为城市开始发展，军校就搬走了，他们就把军官的高等教育分开了。

And then, I think that was by the second year that I was in the school, second or third year, that became that because the city started to grow and then military school was wrong, and then they separated the higher education for military officers.

他们分开了，把那些人安排到了别的地方。

They separated them and they put them in a different place.

但那个动物园后来成了基多首都的第一个动物园。

But that zoo actually became the first zoo of the capital of Quito.

等等。

Wait.

所以你们学校有个动物园，里面还有狮子？

So you had a zoo with lions at your school?

是的。

Yes.

你说你能看到狮子，那它们大概也能看到你吧。

And you said you could see the lions in And your they could see you presumably.

对。

Yeah.

大概看不到吧。

Probably not.

对。

Yeah.

我觉得它们应该能看到你。

Well, I assume they could see you.

狮子的视力挺好的。

Lion vision is pretty good.

我不知道具体有多清晰，但我觉得它们应该能看到。

I don't know what the resolution is, but I'm guessing that their Yeah.

视觉方面，它们确实主要靠嗅觉，但它们也是基于视觉的捕猎者。

Vision they definitely use their olfaction, but they are site But based hunters as

我特别记得一个场景，就是爬上去的时候。

I have specifically one memory, like climbing up.

我想那可能是因为我们有一个奥林匹克标准的游泳池，还有各种活动。

I think it was like from the because we had an Olympic pool and we had all of these events.

那个足球场是国家队训练的地方，因为他们没有自己的训练场地。

The soccer field was the field where the national team will go and train on because they didn't have their own training grounds.

后来他们有了自己的训练场地。

Later on, they had their own training grounds.

但那是你慢慢习惯的事情，对吧？

So, but that was something that you just grow into it, right?

就像，但那是经过多年，尤其是现在，我才能反思这些。

Like, but it was with the years and now especially, like, that I get to reflect on it.

通过那段经历和那种教育，我真的是非常幸运。

I was extremely fortunate through that experience and that education.

而现在，我在这里分享一些我的故事。

And now, I'm here sharing some of the story.

希望这能激励一些人，尤其是那些想追逐梦想的年轻人。

And hopefully, through that inspiring some people, especially young people that would like to go and chase their dreams, you know.

所以，你在厄瓜多尔上的是军校。

So you you went to military school in Ecuador.

对。

Yeah.

你毕业后，决定去……

You graduated and you decided to go to

对。

Yeah.

所以，在军校里，他们会挑选顶尖的学员，我记得大概是前10%，然后让他们接受特殊训练。

So, about to become a So, in the military school, they will select the top cadets, like I think it was the top 10%, and they will select them and they will put them through a special training.

所以，你基本上只有一半的暑假时间。

So, you have essentially being half like what was a normal summer vacation.