Susanne Aufreiter

Products of the Colonic Microbiota Mediate the Effects of Diet on Colon Cancer Risk

It is estimated that most colon cancers can be attributed to dietary causes. We have hypothesized that diet influences the health of the colonic mucosa through interaction with the microbiota and that it is the milieu interior that regulates mucosal proliferation and therefore cancer risk. To validate this further, we compared colonic contents from healthy 50- to 65-y-old people from populations with high and low risk, specifically low risk Native Africans (cancer incidence <1:100,000; n = 17), high risk African Americans (risk 65:100,000; n = 17), and Caucasian Americans (risk 50:100,000; n = 18). Americans typically consume a high-animal protein and -fat diet, whereas Africans consume a staple diet of maize meal, rich in resistant starch and low in animal products. Following overnight fasting, rapid colonic evacuation was performed with 2 L polyethylene glycol. Total colonic evacuants were analyzed for SCFA, vitamins, nitrogen, and minerals. Total SCFA and butyrate were significantly higher in Native Africans than in both American groups. Colonic folate and biotin content, measured by Lactobacillus rhamnoses and Lactobacillus plantarum ATCC 8014 bioassay, respectively, exceeded normal daily dietary intakes. Compared with Africans, calcium and iron contents were significantly higher in Caucasian Americans and zinc content was significantly higher in African Americans, but nitrogen content did not differ among the 3 groups. In conclusion, the results support our hypothesis that the microbiota mediates the effect diet has on colon cancer risk by their generation of butyrate, folate, and biotin, molecules known to play a key role in the regulation of epithelial proliferation.

Mineral and chemical analyses of soils eaten by humans in Indonesia.

Five Javanese soil samples, including three earths eaten by humans as therapeutic medicine, were analyzed for their physical, mineral and chemical properties along with suitable control samples (not eaten). The eaten soils have a high content of hydrated halloysite and kaolinite, that is, clay minerals that are pseudoforms of the pharmaceutical Kaopectate™. Along with hydrated halloysite in a ratio of nearly 1:1, the expandable clay mineral smectite is also present, but in much greater quantity than is usually found in Kaopectate™. Among the chemical elements that may act as a stimulus for geophagy, only Na, Mn, K and S are possible candidates driving this behavior. Sodium is inherent in the minerals derived from the volcanic bedrock; and it is present in a form other than NaCl. Iron, which is often higher in soils eaten by both human and nonhuman primates, and has therefore been regarded in the past as a possible stimulus for geophagy, is relatively high in these soils, but does not have a higher concentration in the eaten soils relative to the uneaten soils in this group of samples. Cobalt and chromium, two important trace elements in human nutrition and diet, are marginally but not markedly higher in the eaten samples. The eaten soils in all cases have predominantly higher levels of 1:1 clay minerals than the 2:1 minerals which may predominate in some of the control soils, which some studies have associated with health problems. Soils can adsorb dietary toxins, present in the plant diet or those produced by microorganisms. Taking the toxic alkaloids quinine, atropine, sparteine, and lupanine as examples, it is evident that soils from Ampo (southern Java) have a very good adsorptive capacity, comparable to that of coal or charcoal. Other Javanese soils also adsorb these toxins, but to a lesser degree.

Mountain gorilla geophagy: A possible seasonal behavior for dealing with the effects of dietary changes

Geophageous Rwandan mountain gorillas excavate and eat weathered leucite-rich regolith (subsoil C horizons) from the slopes of Mount Visoke in the Virunga Mountains. In the months of the dry season, the gorillas reportedly ingest a halloysitic natural earth having a chemical composition similar to that of Kaopectate, a pharmaceutical used by humans to treat gastrointestinal upsets. Several plants known to contain potential toxins are consumed more heavily by gorillas in these months. New information from geochemical and mineral analyses suggests that geophagy may alleviate intestinal problems associated with changes in their diet because the ingested weathered regolith,containing halloysitic clay minerals, may act as a pharmaceutical agent that helps to adsorb toxins and to control dehydration in the dry season.

High concentrations of folate and unmetabolized folic acid in a cohort of pregnant Canadian women and umbilical cord blood

BACKGROUND Mandatory fortification, prevalent supplement use, and public health guidelines recommending periconceptional supplementation have increased folic acid intakes in North American pregnant women. However, the effects of increased folic acid intakes during pregnancy on maternal and cord blood folate concentrations have not been well established. OBJECTIVES In this prospective study, we determined maternal and cord blood concentrations of folate and unmetabolized folic acid (UMFA) in a cohort of pregnant Canadian women and their newborns and examined the effect of maternal intakes of folate and folic acid and fetal genetic variants in folate metabolism on folate status. DESIGN Folate and folic acid intakes of 368 Canadian pregnant women were assessed in early (0-16 wk) and late (23-37 wk) pregnancy. Blood concentrations of folate and UMFA were measured with the use of immunoassays and liquid chromatography-mass spectrometry, respectively, in maternal samples in early pregnancy (12-16 wk), at delivery (28-42 wk), and in cord blood. Four fetal genetic variants of the 5,10-methylenetetrahydrofolate reductase (MTHFR) and dihydrofolate reductase (DHFR) genes were assessed for their association with cord blood concentrations of folate and UMFA. RESULTS Geometric mean (95% CI) maternal red blood cell (RBC) folate concentrations were 2417 nmol/L (2362, 2472 nmol/L ) and 2793 nmol/L (2721, 2867 nmol/L ) in early pregnancy and at delivery, respectively. The mean (95% CI) cord RBC folate concentration was 2689 nmol/L (2614, 2765 nmol/L). UMFA was detectable in >90% of maternal and cord plasma samples. Although 3 fetal MTHFR and DHFR genetic variants had no effect, the fetal MTHFR 677TT genotype was associated with significantly lower cord serum (P = 0.03) and higher cord RBC (P = 0.02) folate concentrations than those of the wild type. CONCLUSIONS Notwithstanding differences in assays, maternal and cord RBC folate and plasma UMFA concentrations were higher than previously reported values. Functional ramifications of high folate and UMFA concentrations in maternal and fetal circulation warrant additional investigation because an excess folate status may affect long-term health outcomes of the offspring. This study was registered at www.clinicaltrials.gov as NCT02244684.

The adaptive significance of geophagy for Japanese macaques (Macaca fuscata) at Arashiyama, Japan

We gathered data on the amount, composition, and rate of ingestion of foods and soils by the provisioned Japanese macaques (Macaca fuscata fuscata) at Arashiyama, Japan. Behavioral observations spanned one year on 8 adult females, using focal animal sampling. We analyzed a subsample of their foods for nutritional and toxic secondary compound content. We also analyzed soils eaten by the macaques for several physical-chemical properties and tested their adsorption affinity to tannins and alkaloids. Geophagy occurred at a high rate of 2.97 g/indiv./day with an elevated frequency in the afternoon. About two-thirds of their foods (by fresh weight) were provisioned items, which are extremely rich in proteins and soluble carbohydrates. The soils that they ingested were generally poor in mineral elements, the bio-availability of which was low. The soils had a high adsorption capacity for plant alkaloids but were poorly absorptive for tannins. They were rich in clay minerals of proven buffering capacity. Geophagy at Arashiyama may improve the health of macaques via buffering gastric upset. We discuss the results from the viewpoint of several hypotheses on geophagy.

Mineralogical and chemical interactions of soils eaten by chimpanzees of the Mahale mountains and Gombe stream National Parks, Tanzania

Termite mound soils eaten by chimpanzees of the Mahale Mountains and Gombe National Parks, Tanzania, have mineralogical and geochemical compositions similar to many soils eaten by higher primates, but release very low levels of either toxic or nutritional inorganic elements to solution at acid pH. Comparison with control (uneaten) soils from the same areas showed lower levels of carbon and nitrogen in the eaten soils, a relationship confirmed by surface analysis. Surface analysis also revealed lower levels of iron on particle surfaces versus interiors, and higher levels of iron on ingested versus control soil particle surfaces. The soils can adsorb dietary toxins, present in the plant diet or those produced by microorganisms. Taking the toxic alkaloids quinine, atropine, sparteine, and lupanine as examples, it is evident that soils from Mahale have a very good adsorptive capacity. A new adaptive advantage of geophagy is proposed, based on the prevention of iron uptake. The behavior of the soils in vitro is consistent with the theory that geophagy has a therapeutic value for these chimpanzees.

Soils Consumed by Chimpanzees of the Kanyawara Community in the Kibale Forest, Uganda

We previously reported on a study of 4 soils that chimpanzees of the Kanyawara community in the Kibale National Park, Uganda consumed on a near-daily basis. We suggested that iron was a possible chemical stimulus in association with high quantities of Si:Al = 1:1-dominated clay minerals in the consumed material. To test our initial findings, we analyzed 18 samples from the same general area including 7 samples that the chimpanzees did not eat. Among the chemical elements, As, Au, Br, Ca, Cl, Dy, Mg, Ni, Sb, Sr, and I are below detection limits. Only Fe stands out as a potentially important nutritional element present in sufficient quantity to provide a physiological stimulus for chimpanzees living at high elevations near the flanks of the Ruwenzori Mountains. Along with Fe, metahalloysite is present in high amounts in these soils. In its pure crystalline form as a pharmaceutical grade clay mineral metahalloysite may well counteract the debilitating effects of diarrhea, with an effect similar to what is achieved with kaolinite (cf. KaopectateTM). An unexpected result, the relatively high nitrogen and carbon in the eaten samples relative to the uneaten group, indicates the chimpanzees may have a higher threshold for organic-rich material than previously believed. Contrarily, the color of the ingested material, depicts a material with less humus than in the uneaten group, a finding that is compatible with previous work reported at other geophagy sites in Africa. Of all the choices of soil available to them, the chimpanzees appear to be selecting highly homogeneous chemical natural earths with well-leached and uniform mineralogical material similar to the uneaten group, but with higher relative amounts of clay size material.

Dietary Oligosaccharides Increase Colonic Weight and the Amount but Not Concentration of Bacterially Synthesized Folate in the Colon of Piglets

Recently, we demonstrated that the large pool of folate present in the colon of humans can be absorbed. Here, we investigated whether the net amount of folate synthesized by bacteria in the colon of piglets can be modified by feeding prebiotics to alter their microbial milieu. Male piglets (age 5 d, n = 12) were randomized to a milk-based formula containing either 5 g/L inulin + 5 g/L galactooligosaccharides (IN-GOS) or 5 g/L maltodextrin (control). Body weight did not differ between groups during the 28-d feeding intervention. However, the mean weight of colonic tissue (38%) and their contents (238%) was higher in the IN-GOS than in the control group (P = 0.004, P = 0.0001, respectively). Total bacterial load in the colon of piglets fed IN-GOS was 531% greater and the total amount of folate found in the colon contents was 53% greater than that of controls (P = 0.002, P = 0.02, respectively). Indices of blood folate status (plasma and RBC folate and plasma homocysteine) and folate concentrations in liver and kidneys were unaffected. Both groups exhibited low RBC folate (56 ± 23 nmol/L) and elevated homocysteine (24 ± 7 μmol/L) concentrations, evidence of deficiency if present in humans. In conclusion, dietary supplementation with 5 g of inulin + 5 g of galactooligosaccharides increased the weight, bacterial load, and total folate content in the piglet colon; however, these changes were insufficient to modify indices of whole body folate status. Future studies investigating the impact of feeding prebiotics on localized folate status at the level of the colonocyte are warranted.

The direction of the difference between Canadian and American erythrocyte folate concentrations is dependent on the assay method employed: a comparison of the Canadian Health Measures Survey and National Health and Nutrition Examination Survey.

Fortification of select grain products with folic acid and periconceptional supplementation recommendations in Canada and the USA have improved folate status, and have been associated with a reduced risk of neural tube defects. In the present study, we aimed to conduct a comparison of erythrocyte folate concentrations from the 2007-9 Canadian Health Measures Survey (CHMS) and the 2007-8 US National Health and Nutrition Examination Survey (NHANES). Erythrocyte folate concentration was assessed in participants aged 6-79 years (CHMS, n 5248; NHANES, n 7070). To account for different folate assays employed - Immulite 2000 immunoassay (CHMS) and microbiological assay (NHANES) - a conversion equation was generated (n 152 adults) to adjust the CHMS data. t Tests were used to examine country differences. Median Canadian erythrocyte folate concentrations (method-adjusted) were lower than those of Americans (988 and 1100 nmol/l, respectively), but unadjusted median Canadian erythrocyte folate concentrations were higher (1250 nmol/l). The upper 95% CI boundary of the method-adjusted Canadian erythrocyte folate distribution overlapped that of the American erythrocyte folate concentrations, while the lower 95% CI boundary of the method-adjusted Canadian erythrocyte folate data was below the American distribution. In summary, the fact that erythrocyte folate concentrations were either higher or lower in Canadians compared with Americans, depending on whether an adjustment was made to account for assay differences, suggests that caution must be exercised in evaluating erythrocyte folate data from different countries because analytical methods are not readily comparable. Furthermore, we cannot unequivocally conclude that there are true differences in erythrocyte folate concentrations between the Canadian and American populations in the post-fortification era.

Geophagy by the Bonnet Macaques (Macaca radiata) of Southern India: A Preliminary Analysis

Bonnet macaques (Macaca radiata) in the Marakkanam Reserved Forest of southern India consume termitaria soils. Samples from the ingested termite mounds are compared with samples taken from the surrounding uneaten soils in an attempt to determine why the termitaria soils are eaten. Particle size, clay and primary mineral composition, geochemistry, and scanning electron microscopic analyses are used to search for a possible explanation for geophagy among the bonnet macaques. Kaolin minerals abound throughout the Marakkanam soil sample suite. But the termitaria soils are distinguished by the presence of small amounts of smectite. An abundance of kaolin minerals in combination with small amounts of smectite strongly resembles the mineralogy ofeko, a traditional African remedy for stomach ailments, and Kaopectate™, a western anti-diarrhoeal preparation. The percentage of mature leaves and fruits ofAzadirachta indica consumed by the bonnet macaques is relatively high. Plant feeding deterrents, such as, acid detergent fibre (ADF) and the inherent nature of the fruits ofAzadirachta indica, when consumed in large quantities to act as a purgative, could cause gastrointestinal upsets and diarrhoea. At Marakkanam, bonnet macaques ingest termitaria earth that would act as a pharmaceutical agent to alleviate gastrointestinal upsets and control diarrhoea.