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Ontogenic development continues after birth in mammalian enteric epithelium as an adaptive mechanism to extrauterine life. In the rat, particularly significant developmental changes in enteric structure, function, and cytokinetic properties occur over a short critical period (usually between 16 and 20 days of age), preparatory to dietary change with weaning. Surgical bypass of ileal segments was performed on suckling rats of 12–14 days of age, and the effect on subsequent intestinal development was studied in both the bypassed and the shortened segment remaining in continuity. The bypassed segment, although achieving normal maturational patterns of active sucrase appearance and maltase accumulation, continued to maintain coincident immature patterns of high lactase activity and low cell turnover times. The intestine in continuity showed precocious appearance of active sucrase and accumulation along with maltase to greater than control levels, accompanied by a normal coincident decline in lactase activity and enterocyte life-span. Involvement of intraluminal influences on various parameters of enteric ontogenic development is thus indicated with the effects expressed by a delay in the excluded (bypassed) segment and by stimulation in the shortened segment in continuity. Data are presented in further support of the hypothesis that the life-span of the enterocyte serves postnatally as a primary determinant of enteric lactase levels.

Lactose loading tests and other means were used to determine the pattern of primary "adult" lactose malabsorption (LM) and milk use among 171 subjects, including 122 children and 49 adults, almost all of them Pima Indians of Arizona. LM develops at quite young ages in full-blooded Pima children: already in the 3- to 4-year age group, 40% had LM. Of 62 full-blooded Indians (greater than or equal to 4 years of age), 59 (95%) had LM. Of 41 Indians (greater than or equal to 4 years) who were of mixed Indian-northern European ancestry, however, only 25 (61%) had LM, and, among them, prevalence of LM correlated with degree of northern European admixture. Whereas only 21% of Pima lactose absorbers reported symptoms after the loading test, 72% of malabsorbers did so, with older malabsorbers more likely to experience symptoms. In their everyday lives, only 23% of malabsorbers recognized symptoms brought on by milk consumption, but the percentage of malabsorbers making such an association increased with age. Nevertheless the Pima, adults as well as children, continue to drink reasonable quantities of milk. Family pedigrees are consistent with the hypothesis that adult lactose absorption is inherited as an autosomal dominant trait. Over-all results of this study, moreover, support the geographic hypothesis advanced to explain ethnic or racial differences in prevalence of LM, rather than the induction hypothesis.

Litters of 10-day-old rats and their mothers were placed in specially designed cages which enabled the pups to continue to suckle, not to have access to water, solid foods, or feces, and to ensure that their sole dietary carbohydrate was lactose. The animals were killed at intervals and intestinal β-galactosidases, α-glucosidases, and cellular proliferation were measured. Although the specific activity of intestinal lactase followed the usual decline observed during development, the enzyme was maintained at a significantly higher activity than that of control rats. These animals were also able to hydrolyze lactose more readily as demonstrated by their having a significantly higher concentration of glucose in blood after ingestion of lactose. When segments of intestine were incubated with lactose, glucose plus galactose, sucrose, mannitol, or saline, the decline in the activity of lactase was much less in the presence of lactose than in any of the other media. Thus, the substrate had a stabilizing or protective effect on the enzyme. The developmental pattern of the intestinal a-glucosidases and the "acid" β-galactosidases, and the normal morphological maturation of the intestine were not altered by prolonged nursing and elimination of carbohydrates other than lactose.

Two enzymes of the de novo pathway of pyrimidine biosynthesis, aspartate transcarbamylase and dihydroorotase, and two enzymes of the salvage pathway, uridine kinase and thymidine kinase, were assayed in crypts, villi, and whole intestinal mucosa of the rat during development. Elevated activities of these enzymes could be correlated with active cellular proliferation. The activities of the enzymes were greatest in crypts and decreased as cells migrated along the length of the villi. Also, changes in cellular proliferation during development of intestinal mucosa mirrored changes in enzymatic activities of both the de novo and salvage pathways. In colonic mucosa, where cellular turnover does not increase at weaning, there was no change in activities of these enzymes, offering a biochemical basis for determination of cellular turnover in the intestine.