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From the Neolithic Revolution to Gluten Intolerance: Benefits and Problems Associated with the Cultivation of Wheat

1997; Lippincott Williams & Wilkins; Volume: 24; Linguagem: Inglês

10.1097/00005176-199700001-00005

1536-4801

L. Greco,

Digestive system and related health

WHY ARE THERE SO MANY CASES OF GLUTEN INTOLERANCE? It is difficult to believe that intolerance to one of the most common components of food (bread, pasta) in our environment might provoke such severe immunomediated reactions in any part of the human body. The list is endless, but to attribute malignancies, adverse pregnancy outcome, and impaired brain function to gluten intolerance would seem to be excessive. On the other hand, we have reported on a group of patients affected by drug-resistant epilepsy with cerebral calcifications, half of whom were cured by a gluten-free diet. All of them had atrophic jejunal mucosa, which recovered on a gluten-free diet (1). In addition, we know that the majority of gluten-intolerant subjects, identified by family or population screening, do not have any complaints, although they do have flat intestinal mucosa (2). It seems that a sizable proportion of our population (from 0.3 to 1%) is gluten intolerant and reacts with a wide spectrum of symptoms, from no apparent reaction to severe life-threatening diseases. This intolerance is strongly linked to specific genetic markers that have been selected over thousands of years, while environmental changes, for example, dietary changes, require only centuries to occur. Where do all these cases of gluten-intolerance come from? HUNTERS, FISHERS, AND GATHERERS Human beings have been on earth for over three million years, but Homo sapiens for only about a hundred thousand years. For about ninety thousand years he conducted a nomadic life, obtaining food by hunting, fishing, and collecting fruits, seeds, herbs, and vegetables. Ten thousand years ago the last glaciation came to an end: a neothermal period ensued, which marked the passage from the paleolithic to the neolithic age. The ice gradually melted from the equator to the poles over several thousands of years. While new fertile and humid lands were uncovered in Southeast Asia, all of Europe was still blanketed with ice; the northern countries had to wait up to another four thousand years to get out of a frozen environment. During this period some nomadic tribes started settling down as they developed the ability to gather enough food to store. THE GREAT REVOLUTION The First Farmers The discovery of methods of producing and storing food has been the greatest revolution mankind has ever experienced. In the passage from collection to production of food originated the first system by which human labor gained income over long periods of time. The principle of property was consolidated, and fortifications to protect the land and food stores were developed. Archaeological findings suggest that this revolution was not initiated by the male hunter and warrior, but by the intelligent observations made by women. Women collected seeds, herbs, roots, and tubers. During this activity they probably observed the fall of grain seeds to the ground and their penetration into the soil with rain (3). To our knowledge, the origin of farming practices must be located in the “Fertile Crescent”: the wide belt of Southeast Asia that includes southern Turkey, Palestine, Lebanon, and northern Iraq. In the highlands of this area, abundant rainfall was caused by the neothermal switch. In this area existed, and still exists, a wide variety of wild cereals. The majority of wild cereals had very few seeds (2-4), which easily fell on the ground at maturation. Triticum dicoccoides (wheat) and Hordeum spontaneum (barley) were commonly collected by the local dwellers. The people from the Uadi el-Natuf Tell in Southeast Asia (7800 B.C.) provide the first evidence of a gradual shift from hunting to grain cultivation. Their economy was based on hunting of the gazelle, but their diet also consisted of collected grain seeds. The latter gradually came to form a substantial proportion of their energy intake, as cultivation practices grew. There were no grinding stones or mills, and it is most probable that gathering prevailed on cultivation. But during the Proto-neolithic superior, a cuneiform mortar appeared. One to two thousand years later (5000 B.C.), wild animals formed only 5% of the daily diet, while cereals and farmed animals became a sizable part of it (3). Stable settlements were founded. The village of Catal-Huyuk in southern Turkey had a population of five thousand inhabitants 9000 years B.C. In that area a collection of sickles with oxidian blades, smoothed by routine contact with the siliceous stalks of cereals, has been found. The sickles indicate that it was possible to collect seeds not only by picking them off the ground but also by cutting the stems of plants, which retained the seed in an ear (4). Populations in Mesopotamia developed a great civilization with large cities and powerful armies to defend their lands and food stores. In Egypt a civilization based on farming practices developed in the fifth millennium: they became specialists in the cultivation of wheat, barley (also used to produce beer), and flax. EXPANSION OF THE FARMERS While in Southeast Asia progressive drought made hunting difficult and encouraged farming, in Europe the Paleolithic culture of hunters and gatherers persisted for five thousand more years. In the Fertile Crescent, the availability of food stores and the gradual development of animal farming stimulated an unprecedented demographic explosion. In transmigrations, the mother could carry one infant, while the other family members were obliged to walk. Small children had less chance of surviving. Farmers most probably took advantage of all the hands in the family. In this way the size of families exploded and, as a result, the need to gain more lands was born. The expansions followed the waterways of the Mediterranean and the Danube throughout the times of the Egyptians, Phoenicians, Greeks, and Romans. The farmers' expansion lasted from 9000 B.C. up to 4000 B.C., when it reached Ireland, Denmark, and Sweden, covering most cultivable lands in Europe (5). This expansion was not limited to the diffusion of agricultural practices, but was a migration of peoples characterized by a substantial replacement of the local mesolithic populations of Europe with the neolithic populations of Southeast Asia. More than two thirds of the actual European genetic makeup originates in this new population, while the native genetic background has progressively been lost or confined to isolated geographic areas. The genetic replacement of the native European population is marked by the B8 specificity of the HLA system. Cavalli Sforza and co-workers showed that the migration of farmers is paralleled by the expansion of HLA-B8. The prevalence of HLA-B8 is inversely proportional to the length of time of wheat cultivation. In practice, HLA-B8 appears to be less common in populations that have lived on wheat for a longer time, which seems to be caused by a negative genetic selection in wheat cultivators (6). The incidence of HLA-B8 seems to increase through Europe in a northwesterly direction: the highest incidence of HLA-B8 is found in the indigenous population of the west of Ireland, where wheat cultivation began only 3000 years B.C. and where a very high incidence of gluten intolerance has been reported. EVOLUTION OF CEREALS The early wild cereals of the Triticum (wheat) and Hordeum (barley) species were genetically diploid and carried few seeds, which usually fell on the ground at maturation, making any harvest difficult. A single couple of chromosomes (diploidicity) allowed for a wide genetic and phenotypic heterogeneity with remarkable variations in the content of protein and starches. Poliploid plants occasionally originated in nature but had few chances of surviving without artificial (cultivation) practices and thus were usually lost (7). The beginning of farming, with the use of irrigation, allowed for the survival and expansion of poliploid grains, which reduced genetic variations, causing an increase in genetic uniformity. The first stable formation of poliploid grains dates from about 6000 years B.C. Genetic variability was essential in order to adapt the grains to different environmental conditions (8). Triticum turgide dicoccoides was crossed with Triticum fanschii to create Triticum aestivum, which is the progenitor of all our actual wheat. T. aestivum is an esaploid wheat with 42 chromosomes, versus the 14 chromosomes of T. monococcum. Such powerful grain replaced all existing wheat varieties: over the world there are 20 thousand species of the same unique T. aestivum. For centuries grains had been selected in order to improve their homogeneity and productivity, but soon (in Greek times or perhaps earlier) another quality became desirable. It was necessary for dough to adhere better to improve bread making. Early bread making activities pushed toward cultivation of grains that contained greater amounts of a structural protein that greatly facilitated the bread making: gluten. Over the past two hundred years of our modern age, active genetic selection and genetic manipulation have changed the aspect of the original Triticum enormously, from few grains and a variable content of gluten to abundant grain very enriched in gluten (50% of the protein content), well adapted to cultivation practices, and ready to be handled by machinery. Gluten was not chosen because of its nutritional value (which was unknown at the time and which is far from special, since it is a protein with relatively low nutritional value), but for its commercial qualities. Only a small geographic area (Southeast Asia) developed gluten-containing cereals. In all of Asia rice was cultivated, while in America maize prevailed, as in Africa sorghum and millet had. Rice, maize, sorghum, and millet do not contain gluten. No leavened bread was prepared with them; the majority of mankind never lived on bread. THE RISE OF GLUTEN INTOLERANCE Did everybody adapt to such profound changes in basic nutrition over such a short period of time? Southeastern populations presumably adapted well to the new foods and replaced the mesolithic European dwellers who still lived from hunting and gathering. But a proportion of the local European populations persisted beside the invaders, and some hunters and gatherers did not adapt to the food changes induced by the cultivation of wheat. These people could not recognize gluten as a “tolerable” protein. They may not have had any complaints for centuries, since the content of gluten in the grains they ate was low, but when “industrial” quantities of gluten were introduced to improve bread making, their descendants were exposed to unbearable quantities of an intolerable protein. This population, genetically identifiable by its specific HLA pattern, generated a complex defense mechanism (an immunoresponse) against the gluten, which ultimately is the origin of the damage to their intestines and other organs. These fierce descendants of hunters and fishers, exposed to this subtle enemy, could not develop tolerance and, in the attempt to fight the unknown, ultimately acquired a disease from their excessive defense mechanisms. Acute infectious diarrhea was the main killer of infants in Europe up to fifty years ago, and some 15 babies in every thousand died of this condition. In the suburbs of Naples only twenty-five years ago, 25% of the infant mortality rate of 100/1,000 live births was caused by diarrhea. The vast majority of cases of gluten intolerance occurred among these poor infants. In my own clinical experience twenty-five years ago, I observed several fatal gastrointestinal infections in babies with “celiac crisis,” which has now disappeared from our wards. Despite their lower chances of survival, people with an intolerance for gluten did not disappear. These patients most probably had some selective advantages that counterbalanced the disadvantages of gluten intolerance. Breast-feeding most probably played a major role in preserving some children from the fatal infections of infancy (9). The capacities of breast milk to protect against viral and bacterial attacks, the protection given by maternal antibodies, and the delaying effect on the manifestation of symptoms of gluten intolerance (in the predisposed subjects) may all have benefited the hunters and gatherers, who in this way survived and transmitted their genes. HINTS ON THE EPIDEMIOLOGY OF GLUTEN INTOLERANCE The epidemiology of gluten intolerance, as we know it today, is the complex result of the inheritance of hunters and gatherers. Nutritional attitudes have played a role in the manifestation of gluten intolerance in different parts of Europe: the example of Sweden compared with Denmark or Finland is paradigmatic. Nevertheless, when local incidence rates are compared with other regions' rates, the 95% confidence intervals are so wide that no clear-cut differences can really be shown in the incidence of gluten intolerance in Europe (10). Wherever studies on symptomatic cases have been conducted, an incidence of one case per every 1,000 live births has been reached. Population screening studies invariably come to an incidence rate of one per every 250. This is close to the rate predicted by age-adjusted incidence density studies. We have found our ancestral hunters and gatherers. Their descendants form a substantial proportion of our actual community and deserve a gluten-free alternative, not just as a therapeutic measure but also as an option in normal daily nutrition.