生物与医学2021academic.oup.com
克罗恩病：冷链假说仍然热门吗？
Crohn’s Disease: Is the Cold Chain Hypothesis Still Hot?
进阶 · 约 30 分钟读完前置知识：流行病学基础、胃肠病学基础、微生物组基础
导读
这篇论文重新审视“冷链假说”：即工业化与家庭制冷（冷链）的普及可能与克罗恩病（CD）发病率上升相关，可能的机制涉及低温下仍能存活的微生物。文章比较了多国CD年发病率与家庭冰箱普及率的时间相关性，并讨论这一相关性是否成立、该如何解释。
HN 关注点：HN读者中不少人本身是克罗恩病/IBD患者，且“一个无处不在的现代技术（冰箱）可能与自身免疫病相关”这一设想颇具冲击力，讨论焦点集中在相关不等于因果、微生物组的作用以及患者亲历。
HN 评论精选
这几条评论里：质疑 1 补充 2 亲历 1
质疑论文的生态学相关性证据反直觉（约50%普及率后才可检出），并提示可能是存活率提高带来的诊断增加，而非制冷直接致病。
克罗恩病明确与西方现代生活方式相关。如果冷链假说成立，CD的出现必然与工业和家庭制冷的发展同步。图1A比较了几个国家的年发病率和家庭制冷设备普及率，两者存在时间上的相关性。但值得注意的是，在一个国家，疾病开始可被检出并不是在冰箱开始销售之时，而是要等到约50%家庭配备冰箱之后——这一观察反直觉。这是个有趣的假说，我喜欢这种思路，我们需要更多这类研究。我看到的问题是，制冷总体上应该减少食物中毒和营养不良，并提高脆弱人群的存活率。所以一种可能是，过去在幼年神秘死亡的人现在活得更久，足以被诊断出各种疾病。换句话说，也许现代生活确实导致克罗恩病，也许它只是让这类人存活下来、得到诊断并学会与之共存。
DoreenMichele查看英文原文
CD is definitively associated with the occidental modern way of life 3. If the cold chain hypothesis is valid, the emergence of CD must be parallel to the development of industrial and domestic refrigeration. Figure 1A compares the annual incidence of the disease and the household equipment rate in several countries. There is a temporal correlation between these variables. It should be noted, however, that in a given country the disease begins to be detectable not at the time when refrigerators begin to be sold, but only when about 50% of households are equipped. This observation is counter-intuitive. It's an interesting hypothesis and I like the thinking. We need more of this kind of investigation. The problem I see is that refrigeration should reduce the incidence of food poisoning and malnutrition generally and generally improve survivability of vulnerable populations. So one possibility is that people who used to die mysteriously in early childhood are now living long enough to be diagnosed with various ailments. In other words, maybe modern life does cause Crohn's or maybe it just lets such people survive and get diagnosed and learn to live with their condition.
亲历患者亲历：IBD不等于IBS，饮食和生活方式只能影响症状、不能治愈；对短期研究突破持谨慎态度。
作为克罗恩病患者（17岁确诊，现在有造口），我经常看到人们把它和IBS混为一谈，而IBD绝不是IBS。有趣的是，我参加过一些研究，经历过多次手术，几乎试过所有可用疗法（还有几种可能未来可用的），和一些非常优秀的IBD研究医生合作。我也看到饮食和生活方式确实会影响发作的严重程度，尤其是感受和症状。但它们不能“治愈”克罗恩病或使其缓解。我目前口腔里有炎症，不幸的是你不能像切掉部分肠道那样把它切掉。总之，这类研究来来去去，有些有一丝希望或给研究者提供新方向，但在我几十年的克罗恩病经历中，我已接受：除非运气极好，我这辈子大概等不到治愈。如果真有，它大概也会同时破解许多其他自身免疫病。希望如此！
geerlingguy查看英文原文
As someone with Crohn's (diagnosed at 17, now have an ostomy), I often see a lot of conflation with IBS, which IBD is most definitely not. It's interesting, I've been part of some research studies, I've been through a number of surgeries, and I've literally tried every medical treatment that's available (and a couple that may be someday...) with some very good IBD research docs. And I've also seen that diet and lifestyle choices can definitely affect the severity of a flare, especially the feelings and symptoms. But they cannot 'cure' Crohn's or put it in remission. I currently have inflammation in my mouth, and unfortunately you can't just slice it out to take care of the problem like you can parts of the gut ;) Anyways, all that to say these studies come and go, a few have a sliver of promise or offer some new route for a researcher to go, but in my few decades of Crohn's experience, I've grown to accept that short of a very significant stroke of luck, there probably won't be a cure in my lifetime. And if there is, it'll probably crack the nut on a ton of other autoimmune diseases too. Hopefully!
补充认为微生物失衡（抗生素、缺乏植物纤维）是关键，列举开菲尔、Visbiome、肉食饮食等轶事性缓解案例，呼吁更多临床研究。
如果制冷有助于克罗恩病的发展，我不会感到惊讶。成因可能是多因素的，而且据我自己的研究，微生物（酵母、细菌、真菌）似乎都扮演关键角色。任何以致病方式打破平衡的东西都可能导致功能失调，尤其是抗生素，也包括饮食中缺乏植物细胞壁。每个人都不尽相同，不仅是基因上，还有细菌多样性方面。有少数人通过自制生开菲尔（店里卖的不能比）以及Visbiome（一种有大量研究支持的实验室益生菌）让克罗恩病进入缓解。我还听说短期肉食饮食可能有帮助。克罗恩病似乎没有一致的治疗方法，显然在需要时控制发作的药物是必须的。很多肠道和自身免疫问题似乎都与微生物多样性有关，我期待更多这类临床研究。我们需要一切能得到的帮助。
DantesKite查看英文原文
It wouldn't surprise me if refrigeration contributes to the development of Crohn's disease. The causes can be multi-variate and anecdotally, from my own research, microbes (yeast, bacteria, fungi) all seem to play a key role. Anything that disturbs the balance in pathogenic ways can lead to dysfunction, especially antibiotics, but also a lack of plant cell walls in our diets. Everybody is slightly different, not just genetically, but in terms of the diversity of bacteria. There have been a few people who have managed to put Crohn's disease into remissions with raw kefir produced at home (the ones at store are not comparable) as well as with Visbiome, a probiotic produced in the lab with many studies behind it. And I've also heard the carnivore diet for short durations may help. There doesn't seem to be a consistent way to treat Crohn's disease and obviously, medicine to control flares is a must if the situation demands it. It does seem like a great many gut and autoimmune issues are somehow related to the diversity of microbes though and I look forward to more clinical research like this. We need all the help we can get.
补充把冷链与电灯、噪音、污染等现代环境变化并列，主张以人类尺度设计未来社会，而非回归原始。
自1900年以来，有数量惊人的变化对“现代生活”产生了巨大环境影响，而我们几乎还没弄明白——这个冷链假说对我来说是新的，但它与电灯、城市噪音、空气污染甚至大众识字等巨大变化并列，都是我们 barely 能应对的。我绝对不是主张回到某种原始/高贵的野蛮人理想。但我们可怜的身体进化所适应的环境，与在荧光灯下、坐飞机吃汉堡、盯着屏幕读文字截然不同。未来100年我们建设社会时，应该以人的尺度来建设。
lifeisstillgood查看英文原文
There are a surprisingly large number of changes since ~1900 that have had big environmental effects on "modern life" that we are barely getting to grips with - this cold chain one is new to me but it fits in with electric lighting, urban noise and air pollution and even mass literacy etc as massive changes we can barely get to grips with I am deffo not arguing for some return to some paeleo, noble savage ideal. But our poor bodies evolved for something very different to eating burgers on a plane under flourescent lighting whilst reading text on a screen. Whatever we build as societies in the next 100'years, we should build at human scale.
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