The fermentation process produces large amounts of gaseous by-products, such as methane, carbon dioxide, and hydrogen. This leads to gas build-up in the gut, resulting in cramping and flatulence. In the case of lactase persistence, there is a continued production of lactase at high levels throughout adulthood. Why is the production of lactase regulated in the first place?
Why not just produce lactase in the enterocytes of all adult mammals? The answer is a matter of cellular energetics. Most mammals humans notwithstanding do not consume milk after they have been weaned. Digesting lactose After eating or drinking something containing lactose, the digested food passes from your stomach into your small intestine. Types of lactase deficiency Primary lactase deficiency Primary lactase deficiency is the most common cause of lactose intolerance worldwide.
This type of lactase deficiency is caused by an inherited genetic fault that runs in families. Secondary lactase deficiency Secondary lactase deficiency is a shortage of lactase caused by a problem in your small intestine.
Possible causes of secondary lactase deficiency include: gastroenteritis — an infection of the stomach and intestines coeliac disease — a bowel condition caused by an adverse reaction to a protein called gluten Crohn's disease — a long-term condition that causes inflammation of the lining of the digestive system ulcerative colitis — a long-term condition that affects the large intestine chemotherapy — a cancer treatment long courses of antibiotics The decrease in the production of lactase in secondary lactase deficiency is sometimes only temporary, but it may be permanent if it's caused by a long-term condition.
This is because your body's production of lactase naturally reduces as you get older. Congenital lactase deficiency Congenital lactase deficiency is a rare condition that runs in families and is found in newborn babies.
The mutations are believed to interfere with the function of the lactase enzyme, leading to undigested lactose in the small intestine and causing severe diarrhea. Lactose intolerance in adulthood is caused by gradually decreasing activity expression of the LCT gene after infancy, which occurs in most humans. Genetics Home Reference has merged with MedlinePlus.
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The expression of intestinal lactase is under developmental regulation. In humans, intestinal lactase activity starts to increase during the third trimester, eventually reaching its peak at birth 1. Healthy infants usually exhibit high lactase activity, but the postweaning period sees the emergence of 2 phenotypes: lactase deficiency and lactase persistence. In lactase-deficient individuals, lactase expression begins to gradually decrease some time during childhood, eventually making them incapable of digesting dietary lactose.
This condition is referred to as adult-type hypolactasia. The age of onset for hypolactasia varies considerably between individuals and populations with some children exhibiting low lactase concentrations at as young as 2 y of age 9. In contrast to lactase deficiency, lactase-persistent individuals continue to express high lactase activity after childhood i.
The phenotypic differences between adult-type hypolactasia and normolactasia are explained by genetic polymorphism. The CC genotype implies reduced lactase activity, whereas the TT genotype is associated with normolactasia. Also, individuals with the CC genotype show varying lactase activities, suggesting that some lactase-deficient individuals might be better at digesting lactose than others Despite the relatively well-characterized genetics of lactase deficiency, the exact molecular mechanisms behind the genetically programmed decline in lactase expression remain only partially understood.
In normolactasia, when intestinal lactase is high, only a small percentage of ingested lactose reaches the colon However, when intestinal lactase activity is low, lactose escapes absorption in the small intestine, thus subjecting it to colonic fermentation.
The colonic fermentation process might explain why certain lactase-deficient individuals experience intolerance symptoms to lactose whereas others do not Together with undigested lactose, the rapid accumulation of fermentation products increases the osmotic load in the colonic lumen, leading to intolerance symptoms after lactose intake Researchers and clinicians have employed several methods to assess an individual's ability to absorb dietary lactose Clinically, these methods are important because they can be used to exclude lactose intolerance when diagnosing functional GI disorders.
Intestinal lactase activity can be measured directly from intestinal biopsies or indirectly with a lactose challenge. Although direct measurement is the reference standard, obtaining biopsies is invasive and rarely available, making indirect measurements more practical for routine assessments. The 2 most frequently used indirect measurements of lactase status are the lactose tolerance test LTT and the H 2 -breath test In both tests, a subject is challenged with an oral dose of 20—50 g lactose after which blood glucose concentrations LTT or H 2 concentrations in expiratory air are measured for every 30 min for 2—3 h.
In contrast, the H 2 -breath test is based on the activity of colonic microbes: when lactase activity is low, unabsorbed lactose enters the colon where colonic microbes produce H 2 via a fermentation process. If breath H 2 concentration rises 20 ppm above pretest values, it is regarded as a sign of reduced lactase activity.
Both the LTT and the H 2 -breath test are susceptible to confounding factors but the major advantage of these tests is that they allow symptom assessment during testing so they can also be used to diagnose lactose intolerance The first experiments on the induction of intestinal lactase in response to dietary lactose intake were conducted as long ago as the beginning of the 20th century when researchers fed different animal species milk or lactose and analyzed changes in their lactase activity.
Although these experiments relied on cruder analytic methods than today, they showed that lactose feeding does not induce intestinal lactase activity in adult mammals Subsequent animal studies with modern methods of analysis have produced conflicting findings, with some studies showing increased intestinal lactase activities following lactose feeding 23—28 , whereas others have reported no such effect 29— In humans, studies attempting to induce intestinal lactase with different lactose feeding protocols have consistently produced negative findings Table 1.
Cuatrecasas et al. Similarly, in by far the largest study in terms of subjects, Keusch et al. Smaller studies and case reports with various lactose-feeding protocols have reported similar findings 36— In the only intervention study conducted exclusively in children, feeding 25 g of lactose daily for 1 y did not improve lactose absorption in lactose-malabsorbing children Additionally, lactose feeding did not seem to prevent the decline in lactose-absorbing capacity because 5 of 8 previously lactose-absorbing children became lactose-malabsorbers during the intervention.
Intervention studies investigating changes in intestinal lactase activity in humans after a lactose feeding period or a period of lactose withdrawal 1. Intervention studies where lactose is eliminated from diet are scarce and have produced somewhat conflicting results Table 1.
In 1 of the subjects, the lactose absorption capacity fell almost to half of the baseline value after only 2 mo but did not decline further. In this study lactose absorption capacity was measured as lactose absorption ratio, whereby the rise in blood glucose concentration after lactose intake is expressed as a percentage of the rise in blood glucose after ingesting a solution containing an equal amount of glucose and galactose Notably, although both subjects exhibited decreased lactose absorption capacity after the intervention period, both would still be classified as lactose-absorbers according to the established cut-off value In another study, removing lactose from the diet of 6 healthy lactose-absorbers for 42 d produced varying results: intestinal lactase activity increased in 2 subjects and decreased in 3 However, these changes did not affect the results of the LTT, leading the authors to speculate that the observed fluctuations in lactase activity likely resulted from variations in the location of the biopsy specimen This is a reasonable assumption considering the spatial differences in intestinal lactase expression and that other intestinal disaccharidases followed a similar pattern in their analyses.
Furthermore, all subjects whose intestinal lactase activity decreased during the study still exhibited sufficient lactase activity and experienced no GI symptoms during the LTT, indicating that lactose withdrawal did not affect their ability to process dietary lactose Taken together, the results from intervention studies show that intestinal lactase activity is not modified by the presence of lactose in the diet.
Cross-sectional studies offer another way to investigate the possible relation between lactose absorption and lactose intake. Obviously, this type of study cannot establish causality, i. On a global level, populations with a high prevalence of lactase deficiency consume less lactose-containing dairy products than populations where lactase persistence dominates 3 , This most likely echoes the culture-historical theory of population-level adaptation, gradually leading to a high prevalence of lactase persistence in cultures where dairy products are commonly available for nutrition.
However, on an individual level, milk or lactose consumption appears to be a poor indicator of a person's lactose absorption status. Lactose absorption capacity enzyme activity or LTT shows no correlation with daily milk intake in several populations 36 , 46— Also, studies have identified multiple individuals incapable of absorbing lactose despite regular daily milk consumption 48 , 51—54 or lactose-absorbing individuals who have consumed no or little milk products after weaning 46 , 48 , 55— For example, in a y follow up study, Sahi et al.
In their study cohort, all previously identified lactose-malabsorbers also remained as such during the y follow-up period even though some of them continued consuming milk regularly. One notable exception to the aforementioned studies is a report from Bolin and Davis 58 describing a lower incidence of lactose malabsorption in Australian-born Chinese than indigenous Chinese living in Singapore. Nevertheless, the overall evidence from cross-sectional studies seems to support the findings of the intervention studies that lactose absorption capacity does not depend on the availability of dietary lactose.
Considering that the age of onset for lactase deficiency varies considerably between populations, studies examining the relation between milk consumption habits and intestinal lactase activity in young children are especially interesting.
Cook 59 reported that Ugandan children exhibited a gradual fall in lactose absorption capacity from birth to childhood irrespective of their milk intake. Similarly, in a study conducted in Thailand, continuous milk intake since infancy did not prevent a decline in lactose-absorbing capacity Furthermore, studies on Peruvian and Israeli children reported that the lactose-absorbing capacity in these populations was not related to milk consumption during childhood 61 , On the other hand, others have suggested that although lactase status is genetically determined, continued lactose intake after weaning could increase the age of onset for hypolactasia 51 , This is mostly supported by data showing that in populations where milk consumption is high, hypolactasia appears at a later age than in populations with low milk consumption 39 , 51 , 54 , 59 , 60 , 62— In a study cohort consisting of Mexican-American children and Anglo-American children, lactose malabsorption manifested earlier in the Mexican-American group who also consumed less milk than the Anglo-American children Bolin et al.
However, the causality of this relation is uncertain. In the only intervention study conducted in young children, milk supplementation for 1 y did not prevent or delay the development of hypolactasia This study was conducted in a Singaporean population where the prevalence of hypolactasia is high. Possibly, the observed variations in the age of onset for hypolactasia in different populations are under generic or epigenetic regulation and lactose intake does not influence this process.
Although endogenous lactase activities remain unchanged during lactose feeding, lactose-malabsorbers frequently report experiencing fewer and less severe GI symptoms as feeding progresses. This would suggest that some adaptive mechanisms relating to lactose processing occur during prolonged intake of lactose. In one of the first studies to demonstrate adaptation to lactose feeding, Johnson et al. In addition, when challenged with the maximum tolerated dose of lactose, 4 of these subjects exhibited no increase in breath H 2 concentration Subsequent investigations have produced similar findings: lactose-malabsorbing individuals show decreased breath H 2 concentrations after a lactose challenge following a lactose-feeding period 68—71 Table 2.
Although these reports have reported none or only minor improvements in GI symptoms, the findings imply that colonic microbes adapt to the presence of lactose in the colonic lumen. Interestingly, these bacterial taxa do not produce H 2 during carbohydrate fermentation, which likely explains the observed reduction in breath H 2 concentrations after lactose feeding These results suggest that when dietary lactose reaches the colon, it stimulates the growth of lactose-fermenting bacteria, but whether this reduces intolerance symptoms to lactose is still a matter of debate.
Studies have shown decreased flatulence during a lactose challenge following a lactose-feeding period, possibly because of microbial changes leading to reduced colonic gas production 68 , Colonic adaptation is also supported by a study showing that supplementing lactose-intolerant individuals with a prebiotic increases the proportion of lactose-fermenting bacteria, which leads to decreased abdominal pain when lactose is reintroduced in the diet 75 , Taken together, however, these studies mainly report only minor improvements in 1 intolerance symptom with no changes in other GI symptoms 68 , 70 ,
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