Further insights into mucosal adaptation

248

SELECTED

SUMMARIES

GASTROENTEROLOGY

yogurt has been labeled

an “autodigesting” type of milk product (N Engl J Med 1984;310:1-3). Heating or pasteurizing the yogurt to increase its shelf life markedly diminishes the lactase activity by destroying the viability of the organisms (J Dairy Sci 1984;67:1-6, Am J Clin Nutr 1987:45:570-4). It is of interest that two other cultured milk products, buttermilk, also produced by a fermentation process, and milk containing Lactobacillus acidophilus (sweet acidophilus milk], do not have the same enzyme property as yogurt and caused symptoms in some susceptible subjects (Am J Clin Nutr 1984;40:1219-23). The data of Martini et al. answer the second question concerning differences among yogurts in the affirmative, by showing for the first time that unflavored yogurt caused less of a change in breath hydrogen than did strawberry yogurt and that commercial unflavored yogurts generally had higher P-galactosidase activity than flavored ones. However, in their study, no symptoms were reported by lactose-deficient volunteers after the flavored yogurt, despite the larger change in breath hydrogen. This finding points up the fact that multiple factors are probably involved in the production or prevention of symptoms in lactase-deficient people, including the physical state of the material ingested, the effect of the foodstuff on gastric emptying, the substances produced by the cultured bacteria while in the small intestine, and the variety of gases

released

during

fermentation

in the colon

(Am J Clin Nutr

1984;40:1219-23). Because

frozen

and her group with

breath

deficient

dairy

tests

patients

their study,

products

are extremely

at the University and

of Minnesota

symptom

tolerate

them.

pasteurization

popular, decided

recording

whether

The answer

of yogurt

1, had

symptoms.

elevated

breath

Moreover,

the

tests, addition

before

and

lactose-

was generally freezing

shelf life led to zero P-galactosidase activity Lactose-intolerant people ingesting this product, gurt

Martini

to evaluate no. In

to increase

the

in the product. i.e., frozen yo-

3 of 8 volunteers

of a starter

had

culture

to the

product

so that the frozen yogurt would be labeled as having as in frozen yogurt 2, did not change the “active culture,” @-galactosidase activity sufficiently. Lactose malabsorption and symptoms

freezing with

were

seen in 2 of 8 volunteers.

process

freezing

itself

as destructive

at a lower

temperature.

Their

data identify

of /.Qalactosidase -70°C.

i.e.,

the

actilfity, preferable

to

-14°C further

for preservation of some enzyme activity. The enzyme is reduced by repeated freezing and thawing. Only frozen

yogurt

3, which

had a starter

of P-galactosidase

after

culture

pasteurization

added

to it with a high level

but

before

freezing,

had

sufficient P-galactosidase activity to prevent intestinal symptoms and produce significantly less hydrogen (p < 0.05) than the other frozen products. Unfortunately, as Martini et al. point out, a product

like this is not commercially

Finally,

the data

milk, despite their to fewer symptoms. product,

although

the results. 111summary, with dairy

of Martini

available

et al. show

that

at present. ice cream

and ice

high levels of fat and milk solids, did not lead Two of 8 volunteers had symptoms with each the portions

this article

tested

provides

lactose-intolerant patients products and their potential

were large, perhaps a rational

the various for causing

skewing

basis for discussing yogurt and frozen side effects. On the

basis of the data presented these patients will most likely tolerate flavored as well as unflavored yogurts. Unfortunately some of them will certainly have symptoms after ingesting ice cream, ice milk, or frozen yogurt. Making ice cream or ice milk from lactase-treated milk (Paine DM, Bayless TM, eds. Lactose digestion, Baltimore: Johns Hopkins University Press, 1981:252-6) may decrease symptoms. A further advance in the tolerance of frozen yogurt yogurt

could also be made if this article’s suggestion that frozen be produced by adding active culture with a high level of

P-galactosidase

after pasteurization

by the companies

but before

Vol. 95, No. 1

freezing

is heeded

making this product. t1. SHIELDS. M.D.

FURTHER INSIGHTS INTO MUCOSAL ADAPTATION Chaves M, Smith MW, Williamson RCN (Department of Surgery, University of Bristol, Bristol and AFRC, Institute of Animal Physiology, Babraham, Cambridge, U.K.) Increased activity of digestive enzymes in ileal enterocytes adapting to proximal small bowel resection. Gut 1987;28: 981-7 (August). The authors examined adaptability of two digestive enzymes in rat ileal enterocytes after 60% proximal small bowel resection. There were two control groups in which the small intestine was transected and rejoined in either ileum or jejunum without removal of tissue. Food and water were allowed ad libitum. Three weeks after resection or transection tritiated thymidine was injected intraperitoneally 2, 10, 20, 30, or 40 h before the animals were killed by cervical dislocation. A &cm intestinal segment, 2-6 cm distal to the anastomosis, was removed. Half of each segment was used for measurements of enterocyte migration rates by autoradiography. The other half was used for cytochemical determinations by scanning microdensitometry of a-glucosidase and neutral aminopeptidase activities. Changes in enzyme activities recorded along the length of the villus were computer-fitted by logistic growth curves. Comparisons were made between enzyme activities found in enterocytes at similar positions on the villus surface. Relations between enzyme activity and enterocyte age were also examined. Resection increased ileal villus height by 81”/” and crypt depth by 340/o compared with transection. Values for ileal remnants remaining after resection were also 39%41%) greater than those for jejunum from transected controls. In resected ileal remnants cu-glucosidase activity in crypts was greater than controls and increased threefold to fourfold over the first 250 pm of villus surface. There was a pronounced fall in enzyme activity as the enterocyte migrated further toward the villus tip. This rise and fall also occurred in control ileal villus enterocytes but was much less noticeable. Aminopeptidase activities in crypts of resected ileal remnants were greater than in ileal control tissues. Activities increased with enterocyte migration in both resected and control groups but at different rates, so that by 250 pm of villus surface aminopeptidase activities were the same. Enzyme activities declined during further enterocyte migration and activities at the villus tips were the same in both resected and control groups. As the villus was longer in ileal remnants from resected animals, the decline in aminopeptidase was less steep in ileal remnants than in controls. Enterocyte migration rates were linearly related with time in both control and ileal remnant tissues, but migration was faster in ileal remnants. In relating enzyme profile to enterocyte age both a-glucosidase and aminopeptidase activities appeared earlier in ileal remnants, with a fourfold increase in enzyme activities by 10 h. Over the subsequent 10 h the rate of appearance of

aminopeptidase was taster in control tissues, whereas the opposite occurred for cu-glucosidase. The net effect by XI h was that enterocytes from remnant and control ilea had the same aminopeptidase activities, but ileal remnant tissues exhibited a fourfold greater a-glucosidase activity than control ileum. In enterocytes from jejunal tissues, LYglucosidase activities were intermediate between control ileum and ileum remaining after resection at the cryptvillus junction. As enterocyte migration occurred along the villus. activities increased and then decreased, so that values at the jejunal villus tips were similar. Jejunal aminopeptidase activity was slightly higher than that found in c:ontrol ileum and ileal remnants. Integrative aspects of enterocyte development (change of enzyme activities with age) showed that the time for maximal ru-glucosidase activity after resection decreased from lti to 10 b. For aminopeptidase activity the change was less pronounced (13 to 9 h). The corresponding times for maximal enzyme expressions for jejunal enterocytes (12 and 1’1 h) were intermediate between ileal controls and remnants. Absolute values for the maximal rate of LYglucosidase appearance showed a sixfold increase after resection, but corresponding data for aminopeptidase showed a slight decrease. Thus for cu-glucosidase the change in rate of appearance rather than the reduced time to express this enzyme at maximal rate is of prime importancc: in determining the overall magnitude of this adaptive response. As a final step the authors calculated total enzyme contents using villus surface areas. Adaptation of aminopeptidase was largely through a threefold increase in surface area. For cr-glucosidase, adaptation occurred by both an increased surface area and an increase in the ability of individual enterocytes to express this enzyme in their

brush

bortler

of enterocyte functions after resection is therefore useful. A decreased functional specific activity together with faster enterocyte migration and shortened life span has led to the hypothesis that postresection adapted enterocytes mav be func.tionally immature (Gastroellterology 1971:60:6Y-75, Kes Exp Med (Ber)) 1978;173: 41-53. J Physiol (Land] 1~83;334:213-2:j]. Responses of enterocytes are known to vary according to metabolic: function, nutrient demand. and nutrient load. An area only partly explored is the effects that the taller villi after resection may have on the thickn~ss ot the unstirred water layer. l~urthermorc:. effects of diet and therefore effects of different luminal content:; on the unstirred layer in the postresected state remain ill-d& Ined. These factors ccould drastically affec.t intestinal uptake rates, particularly where the unstirred layer is the rate-limiting facior for uptake of a luminal nutrient. For example, it has bwn shown that the thir:kness of the unstirred layer in diabetic. rat intestine increases on a loll-cholesterol diet and decreases 011 a higtl-carbohydrate diet [Am J Physiol 1983:245((;astrointf!st Liver f’hysiol 8):G443-fiZ. Am J (Olin Kutr 1983:38:394&403. Dig Dis %i 1986;31:19:1-201). To add c:omplexity, newer Ivork has also indicated that there is not only- a separation between mu~osal grolvth and functional adaptation but also regional differences in mechanisms controlling growth and function /Am J Phvsitrl lYt%3:244(Gastrointest Liver Physiol 7):G295-300. (;astroenterolog!: 1985;89:1026-34. Am 1 Physiol 1986:251(Gastrointest Liver Phvsiol ‘14):G124-31. G370-4. G460-6, Pediatr Kes 1987:22:2!)-33. Gastroenterologl lY87:Y3:295-300]. The study summarized above examined integrative aspects, the appearance and total villus contents of two brush border enzymes in the postresection animal. There are clear differences in adaptations of the two enzymes examined. and the findings contradict the comfortable concept of enterocgtc immaturity. The overall message of my comments is that mechanisms of adaptation at the cellular level are complex. Ilnraveling them fully will occupy investigators for some time yet, but should prove to be interesting and worthwhile.

membranes.

This VOX marks 100 yr since the first description of Comment. adaptive changes followin:: intestinal resection in vertebrate intestine (Ann Surg 1888:7:YY-115). Anatomic changes in remaining intestine have been dwell characterized, but functional changes as \vr~ll as signals and mechanisms continue to be defined with inc.rrasing specificity [N Engl ] Med 1978;298:1393-402, 1440-50; Adv intern Med 1980;26:265-91. Stand J Gastroenterol lY82;17 (Suppl 741:53-74. Schweiz Med Wochenschr 1985;115:963-70, (;astroentnrolog~ lY8G:Y1:1521-7, Am J Physiol 1986:251(Gastrointest Li\,er Physiol 14):G370-4. G460-61. In the rat. mucosal hyperplasia is well established by 12 days after resection (Gastroenterology lY77:72:701-5) and is proportionate to the amount of intestine rt~movrd (Gastrocntttrology 1977; 72:692-700). Indirect evitlenc~~ suggests that it may take 1-2 mo in the dog and possibly before adaptive changes are fully established up to I vr ill humans [Sc:alltl J Gastroenterol tY82:17(Supp) 74]:53-741. As a result of mucosal adaptation the available surface area of remaining intestine tar nutrient absorption is enlarged. Depending on site and c’xtwlt ol resection it may approach the absorptive area of intact intestine,. (:lini~:ai and laboratory data also clearly show that Iunctional improvement oc.curs with time after resection Even tvith the benefits of parentera nutrition, the absorptive capacit) of remainin:: intt:stine determines overa I1 long-term well being after intestinal resection (Dig Ibis Sci 1986;31:718-231, Functional adaptation ma\~ be thtl result of increased numbers of mucosnl cells. altered iinc.reasetl or det:rrased) functional capacities of adapted mucosal c,ells (brush border enzymes or densities of transport sites). or a combination of both mechanisms. The (.on(:ept of ;rltr!rt~tl (adaptw) spwific: activities versus total activities

ASSESSING

VITAMIN

A STATUS

Campos FACS, Flares H, Underlvood BA (Laboratory of Nutritional Biochemistry, Department of Nutrition, Federal University of Pernambuco. Brazil, and the National Eye Institute. National Institutes of Health, Bethesda, Md.) Effect of an infection on vitamin .4 status of children as measured by the relative dose response (KDR). Am J Clin Nutr 1987;46:91-4. The iauthors had previously validated a relatively noninvasive method of assessing liver vitamin A stores. They showed that after a standard oral dose of retinol the percent increase in blood vitamin A levels expressed as a percentage of the level 5 h after taking vitamin A, called the relative dose response, was indicative of the liver stores of vitamin A. This fact was confirmed in other studies by correlating the relative dose response with liver biopsy. Using this technique they found that after a chickenpox infection children who had previously received a large dose of vitamin A had depleted liver vitamin A stores. Comment. This paper demonstrates an interesting way of studying tissue stores of vitamin A. Such a technique is always welcome as plasma levels of vitamin A mav not be representative