Building and maintaining a homeostatic relationship between a host and its colonizing microbiota entails ongoing complex interactions between the host and the microorganisms. The mucosal immune system, including epithelial cells, plays an essential part in negotiating this equilibrium. Paneth cells (specialized cells in the epithelium of the small intestine) are an important source of antimicrobial peptides in the intestine. These cells have become the focus of investigations that explore the mechanisms of host-microorganism homeostasis in the small intestine and its collapse in the processes of infection and chronic inflammation. In this Review, we provide an overview of the intestinal microbiota and describe the cell biology of Paneth cells, emphasizing the composition of their secretions and the roles of these cells in intestinal host defence and homeostasis. We also highlight the implications of Paneth cell dysfunction in susceptibility to chronic inflammatory bowel disease.

Paneth cells, antimicrobial peptides and maintenance of intestinal homeostasis

The field of probiosis has emerged as a new science with applications in farming and aqaculture as alternatives to antibiotics as well as prophylactics in humans. Probiotics are being developed commercially for both human use, primarily as novel foods or dietary supplements, and in animal feeds for the prevention of gastrointestinal infections, with extensive use in the poultry and aquaculture industries. The impending ban of antibiotics in animal feed, the current concern over the spread of antibiotic resistance genes, the failure to identify new antibiotics and the inherent problems with developing new vaccines make a compelling case for developing alternative prophylactics. Among the large number of probiotic products in use today are bacterial spore formers, mostly of the genus Bacillus. Used primarily in their spore form, these products have been shown to prevent gastrointestinal disorders and the diversity of species used and their applications are astonishing. Understanding the nature of this probiotic effect is complicated, not only because of the complexities of understanding the microbial interactions that occur within the gastrointestinal tract (GIT), but also because Bacillus species are considered allochthonous microorganisms. This review summarizes the commercial applications of Bacillus probiotics. A case will be made that many Bacillus species should not be considered allochthonous microorganisms but, instead, ones that have a bimodal life cycle of growth and sporulation in the environment as well as within the GIT. Specific mechanisms for how Bacillus species can inhibit gastrointestinal infections will be covered, including immunomodulation and the synthesis of antimicrobials. Finally, the safety and licensing issues that affect the use of Bacillus species for commercial development will be summarized, together with evidence showing the growing need to evaluate the safety of individual Bacillus strains as well as species on a case by case by basis.

The use of bacterial spore formers as probiotics

Deoxynivalenol (DON) is a mycotoxin that commonly contaminates cereal-based foods worldwide. At the molecular level, DON disrupts normal cell function by inhibiting protein synthesis via binding to the ribosome and by activating critical cellular kinases involved in signal transduction related to proliferation, differentiation, and apoptosis. Relative to toxicity, there are marked species differences, with the pig being most sensitive to DON, followed by rodent > dog > cat > poultry > ruminants. The physiologic parameter that is most sensitive to low-level DON exposure is the emetic response, with as little as 0.05 to 0.1 mg/kg body weight (bw) inducing vomiting in swine and dogs. Chinese epidemiological studies suggest that DON may also produce emetic effects in humans. With respect to chronic effects, growth (anorexia and decreased nutritional efficiency), immune function, (enhancement and suppression), and reproduction (reduced litter size) are also adversely affected by DON in animals, whereas incidence of neoplasia is not affected. When hazard evaluations were conducted using existing chronic toxicity data and standard safety factors employed for anthropogenic additives/contaminants in foods, tolerable daily intakes (TDIs) ranging from 1 to 5 microg/kg bw have been generated. Given that critical data gaps still exist regarding the potential health effects of DON, additional research is needed to improve capacity for assessing adverse health effects of this mycotoxin. Critical areas for future DON research include molecular mechanisms underlying toxicity, sensitivity of human cells/tissues relative to other species, emetic effects in primates, epidemiological association with gastroenteritis and chronic disease in humans, and surveillance in cereal crops worldwide.

Deoxynivalenol: Toxicology and Potential Effects on Humans

In this paper recent developments in the estimation of frontier functions and the measurement of efficiency are surveyed, and the potential applicability of these methods in agricultural economics is discussed. Frontier production, cost and profit functions are discussed, along with the construction of technical, allocative, scale and overall efficiency measures relative to these estimated frontiers. The two primary methods of frontier estimation, econometric and linear programming, are compared. A survey of recent applications of frontier methods in agriculture is also provided. (This abstract was borrowed from another version of this item.)

Recent Developments in Frontier Modelling and Efficiency Measurement

The trichothecene mycotoxin deoxynivalenol (DON) is produced in wheat, barley and corn following infestation by the fungus Fusarium in the field and during storage. Colloquially known as “vomitoxin” because of its emetic effects in pigs, DON has been associated with human gastroenteritis. Since DON is commonly detected in cereal foods, there are significant questions regarding the risks of acute poisoning and chronic effects posed to persons ingesting this trichothecene. A further challenge is how to best manage perceived risks without rendering critical food staples unavailable to an ever-expanding world population. In experimental animal models, acute DON poisoning causes emesis, whereas chronic low-dose exposure elicits anorexia, growth retardation, immunotoxicity as well as impaired reproduction and development resulting from maternal toxicity. Pathophysiologic effects associated with DON include altered neuroendocrine signaling, proinflammatory gene induction, disruption of the growth hormone axis, and altered gut integrity. At the cellular level, DON induces ribotoxic stress thereby disrupting macromolecule synthesis, cell signaling, differentiation, proliferation, and death. There is a need to better understand the mechanistic linkages between these early dose-dependent molecular effects and relevant pathological sequelae. Epidemiological studies are needed to determine if relationships exist between consumption of high DON levels and incidence of both gastroenteritis and potential chronic diseases. From the perspective of human health translation, a particularly exciting development is the availability of biomarkers of exposure (e.g. DON glucuronide) and effect (e.g. IGF1) now make it possible to study the relationship between DON consumption and growth retardation in susceptible human populations such as children and vegetarians. Ultimately, a fusion of basic and translational research is needed to validate or refine existing risk assessments and regulatory standards for this common mycotoxin.

Deoxynivalenol: mechanisms of action, human exposure, and toxicological relevance.

Two experiments were conducted. In experiment 1, chickens were fed dried Bacillus subtilis var. natto for 3 or 28 days. Growth performance and internal organs were not different from controls, but feed efficiency tended to be improved in the 28-day feeding. In these birds, blood ammonia concentration was decreased (P<0.05). Blood glucose concentration, and amylase and lipase activity in the intestinal content were not significantly different among dietary groups. These results suggest that the B. subtilis natto depressed ammonia concentration. In experiment 2, chickens were fed dietary B. subtilis natto for 28 days. These birds had a tendency to display greater growth performance and intestinal histologies, such as villus height, cell area and cell mitosis, than the controls. Flat cell outline on the duodenal villus surface in controls developed large, protruded cell clusters and cell protuberances after feeding of dietary B. subtilis natto. These results indicate that intestinal function was activated by the depressed blood ammonia concentration in the body of the chicken. The present results may suggest that the B. subtilis natto has the potential to be a beneficial microorganism in chickens.

Histological alterations of intestinal villi in chickens fed dried Bacillus subtilis var. natto.

1. The fine structural alterations of villi and epithelial cells in each part of the small intestine were investigated in layer-type hens fasted for 12 h to 20 d or refed for one day after each fasting period. 2. Within the first 24-h-fasting, villi of the duodenum showed a remarkable reduction in height and those of the jejunum revealed a gradual decrease; such a significant reduction of the villus height was not obtained in the ileum. After 36-h-fasting, villus height in each part gradually decreased with days of fasting. 3. All intestinal villus heights increased after only 1-d-refeeding of various kinds of diets following 3-, 10-, or 20-d-fasting. The duodenum especially rapidly recovered even after long-term fasting of 20 d but the ileum showed very slow recovery, suggesting that the ileum seems to be inactive in absorptive function. 4. These variable alterations of villus height in the proximal intestine suggest that the higher intestinal absorptive ability is under the normal feeding, the more rapidly villus height is influenced by nutritional conditions. 5. Cell area and cell mitosis decreased after fasting, the latter showing a marked reduction. However, in spite of a remarkable decrease of cell mitosis in the proximal intestine after fasting, refeeding activated cell renewal and it soon reached control levels, demonstrating that the villus height mainly varied with the numbers of epithelial cells. 6. In the epithelial cells of the proximal intestine in chickens fasted for 20 d, large lysosomal autophagous vacuoles including mitochondria and dense bodies were observed. These were reduced in size by refeeding for only one day, suggesting that fasting may cause intracellular digestion through lysosomal autophagy. 7. These results lead to the conclusion that long-term for force moulting is possible, that a high protein and high energy diet can be fed immediately after fasting and that a cell undergoing lysosomal autophagy in normal chickens indicates undernutrition.

Effects of fasting and refeeding on structures of the intestinal villi and epithelial cells in White Leghorn hens.

Recovery responses of chick intestinal villus morphology to different refeeding procedures.

1. To obtain intestinal morphological data demonstrating the faster growth rate in broiler (BR) than in White Leghorn (WL) chickens, villi of the duodenum, jejunum and ileum were examined from 1 to 30 d of age by scanning electron microscopy. 2. At the first day after hatching, villi of each intestinal segment showed a finger-like shape in both breeds. Villi developed to a plate-like shape in the duodenum, a wave-like shape in the jejunum and a tongue-like shape in the ileum at 30 d of age via the common plate-like villi at 10 d of age. The fundamental villous shape and arrangement seem to be accomplished by 10 d of age; two types of obliquely elongated plate-like villi showed a zigzag arrangement, adjoining at an angle of 40 degrees to 60 degrees like an oblique T-shape. It is suggested that such a villous arrangement would be more effective for nutrient absorption by inducing a long zigzag flow of ingesta. 3. Compared with WL, even at the first day after hatching BR had many more developed epithelial cell protrusions over the whole apical surface of the duodenal villi. In WL the protrusions were not so apparent and located only in the central area of the villous tip. Furthermore, at 10 d of age BR showed more developed and larger villi, many wider microvilli at the apical portion of villi and more active extrusions of epithelial cells from the tip of the duodenal and jejunal villi. 4. These morphological characteristics of villi in early life in BR suggest a greater absorptive surface area and a more active intestinal function, permitting the faster growth rate of BR immediately after hatching.

Scanning electron microscopic observations on the intestinal villi in growing White Leghorn and broiler chickens from 1 to 30 days of age.

Effects of luminal nutrient absorption, intraluminal physical stimulation, and intravenous parenteral alimentation on the recovery responses of duodenal villus morphology following feed withdrawal in chickens

Koh-en Yamauchi

Papers

Histological alterations of intestinal villi in chickens fed dried Bacillus subtilis var. natto.

Effects of fasting and refeeding on structures of the intestinal villi and epithelial cells in White Leghorn hens.

Recovery responses of chick intestinal villus morphology to different refeeding procedures.

Scanning electron microscopic observations on the intestinal villi in growing White Leghorn and broiler chickens from 1 to 30 days of age.

Effects of luminal nutrient absorption, intraluminal physical stimulation, and intravenous parenteral alimentation on the recovery responses of duodenal villus morphology following feed withdrawal in chickens