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1、对人体细胞和微生物数量的改进估计,Ron Sender,1.Origin of prevalent claims in the literature on the number of bacterial cells In humans,为什么大家会普遍认为肠道微生物数量是人体细胞的十倍,本文作者对文献进行了 追溯,结果显示1977年Savage,annu,Rev.Microbiol引用超过一千。而它的计算基础是 胃肠道容积为1L,肠道微生物浓度为1011 /g.,2.Distribution of bacteria in different human organs,不同部位的微生物数量相差很
2、大,由上表可知,人体微生物约90%都集中 在结肠。 所以作者统计了不同文献的结肠微生物浓度,平均值为0.92*1011 /g.,3.Concentration of bacteria in the colon,4.The number of human cells in a “standard” adult male,A mass-based order-of-magnitude estimate for this number assumes a 10 2 kg man, which is divided by the mass of a “representative” mammalian
3、, cell 10 -12 -10 -11 kg (assuming cell volumes of 1,000-10,000 m 3 , spectively), thus arriving at 10 13 - 10 14 cells.,One study used a DNA-centered method (Baserga, 1985). The method begins by estimating the number of cells in the body of a 25g mouse by dividing the total amount of DNA (stated to
4、 be 20 mg) by the DNA content of one diploid mouse cell(610 -12 g DNA per cell) to get 310 9 cells in a 25 g mouse. Then extrapolate from mouse to human by using the ratio of masses to get 10 13 cells in the human body. This method excludes cells that do not contain DNA, such as red blood cells and
5、platelets.,Summing over a total of 56 cell categories (Bianconi et al., 2013) resulted in an overall estimate of 3.710 13 humancells in the body (SD 0.810 13 , i.e. CV of 22%),5.Updated inventory of human cells in the body,We focus on the six cell types that were recently identified (Bianconi et al.
6、, 2013) to comprise 97% of the human cell count: red blood cell accounting for 70%), glial cells (8%), endothelial cells (7%), derma fibroblasts (5%), platelets (4%) and bone marrow cells (2%). The other 50 cell types account for the remaining 3%.,5.Updated inventory of human cells in the body,Red b
7、lood cells:,(Boer, 1984; Feldschuh and Enson, 1977; Nadler et al., 1962; Snyder et al., 1975) 4.9L,(Ambayya et al., 2014; Dosoo et al.,2012; Nordin et al., 2004; Pekelharing et al., 2010; Volkmer and Heinemann, 2011;Wakeman et al., 2007) 5.010 12 cells/L (SEM 1.2%, CV 7%),(SEM 1.6%, CV 9%),This led
8、to a total of 2.510 13 red blood cells (SEM 2%, CV 12%),This is similar to the earlier report of 2.610 13 cells (Bianconi et al.,2013).,5.Updated inventory of human cells in the body,glial cells : The number of glial cells was previously reported as 310 12 (Bianconi et al., 2013) estimate is based a
9、 10:1 ratio between glial lls and neurons in the brain.,However, a recent analysis (Azevedo et al., 2009) revisits this value and after analyzing the variation in between brain regions concludes that the ratio is close to 1:1. The study concludes that there are 8.510 10 glial cells (CV 11%) in the b
10、rain and a similar number of neurons and so we use these values here.,5.Updated inventory of human cells in the body,endothelial cells : The number of endothelial cells in the body was earlier estimated at 2.510 12 cells (CV 40%), by taking the mean surface area of one endothelial cell (Bianconi et
11、al., 2013) and dividing it into the total surface area of the blood vessels, based on a total capillary length of 810 9 cm. We could not find a primary source for the total length of the capillary bed and thus decided to revisit this estimate. We used data regarding the percentage of the blood volum
12、e in each type of blood vesse (Leggett and Williamst, 1991). Using mean diameters for different blood vessels (Burton, 1954) we were able to derive the total length of each type of vessel (arteries, veins, capillaries etc.) and its corresponding surface area. Dividing by the mean surface area one en
13、dothelial cell (Fltou, 2011) we derive a total estimate of 610 11 cells,5.Updated inventory of human cells in the body,dermal fibroblast: The number of dermal fibroblast was previously estimated to be 1.8510 12 (Bianconi et al., 2013), based on multiplying the total surface area of the human body (S
14、A=1.85 m 2 (Herman, 2007) by an areal density of dermal fibroblasts (Randolph and Simon, 1998). The dermis is composed of two main layers: papillary dermis (about 10% of the dermis thickness) and reticular dermis (the other 90%)(McGrath et al., 2004). 2.6 10 10 cells.,5.Updated inventory of human ce
15、lls in the body,6.Mass centered approach as sanity check for cell count,For a reference man mass of 70 kg, 25% is extracellular fluid (Shen et al., 2007), another7% is extra-cellular solids (Shen et al., 2007), thus we need to account for 47 kg of cell mass (including fat).,作者对人体的细胞数量进行了重新估计,84%为红细胞
16、(质量2.5Kg),5%为血小板; 脂肪占0.2%(质量13Kg),肌肉细胞占0.001%(质量20Kg)。,7.The ratio of bacteria to human cells in the adult body,8.Discussion,we think that updating the ratio of bacteria to human cells from 10:1 or 100:1 to closer to 1:1 does not take away from the biological importance of the microbiota. Yet, we are convinced that a number widely stated should be based on the best available data, serving to keep the quantitative biological discourse rigorous.,经过重新估计后肠道微生物细胞数量与人体细胞数量之比由10