Nanthakumar N Nanda, Dai Dingwei, Newburg David S, Walker W Allan
Developmental Gastroenterology Laboratory, Combined Program in Pediatric Gastroenterology and Nutrition, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts 02129, USA.
FASEB J. 2003 Jan;17(1):44-6. doi: 10.1096/fj.02-0031fje. Epub 2002 Nov 15.
Most enteric bacteria use intestinal brushborder glycoconjugates as their target host cell receptors. It has been postulated that resident microbes regulate specific glycosyltransferases that are responsible for synthesizing brushborder glycoconjugates. To investigate this hypothesis, we measured glycosyltransferase enzyme activities in intestine from different regions of maturing conventional (CONV), germ-free (GF), and ex-germ-free (XGF) mice and compared them to general enzyme markers of gut development, for example, disaccharidases. High alpha2,3/6-Sialyltransferase (ST) activity and low alpha1,2-fucosyltransferase (FT) activities were detected from duodenum to colon in suckling CONV mice, but the relative levels of these activities reversed during the third postnatal wk, rapidly reaching adult levels by the fourth wk. These age-related enzyme changes were significantly attenuated in GF mice, maintaining an immature pattern well past 3 wk. Introduction of gut microflora in GF mice rapidly initiated maturation of glycosyltransferase activity but had no significant affect on developmental programming of dissacharidases. Therefore, in mice, intestinal glycosyltransferase activities are under tissue and developmental control and microflora play a major role in their specific ontogeny but not in overall development. These findings may help explain the regional specificity of commensal bacteria and of enteric pathogens and may also relate age-related changes in microflora to susceptibility to enteropathogens.
大多数肠道细菌将肠道刷状缘糖缀合物作为其靶宿主细胞受体。据推测,常驻微生物调节负责合成刷状缘糖缀合物的特定糖基转移酶。为了研究这一假设,我们测量了成熟的常规(CONV)、无菌(GF)和无菌后(XGF)小鼠不同肠道区域的糖基转移酶活性,并将其与肠道发育的一般酶标志物(如双糖酶)进行比较。在哺乳期CONV小鼠中,从十二指肠到结肠均检测到高α2,3/6-唾液酸转移酶(ST)活性和低α1,2-岩藻糖转移酶(FT)活性,但这些活性的相对水平在出生后第三周发生逆转,到第四周迅速达到成年水平。这些与年龄相关的酶变化在GF小鼠中明显减弱,在3周后仍保持不成熟模式。在GF小鼠中引入肠道微生物群迅速启动了糖基转移酶活性的成熟,但对双糖酶的发育编程没有显著影响。因此,在小鼠中,肠道糖基转移酶活性受组织和发育控制,微生物群在其特定个体发育中起主要作用,但在整体发育中不起作用。这些发现可能有助于解释共生细菌和肠道病原体的区域特异性,也可能将微生物群与年龄相关的变化与对肠道病原体的易感性联系起来。