https://www.thelancet.com/pdfs/journals/lancet/PIIS0140-6736(09)60938-7.pdf

Peptic ulcer disease

Studying the cross talk between nonpathogenic organisms and their mammalian hosts represents an experimental challenge because these interactions are typically subtle and the microbial societies that associate with mammalian hosts are very complex and dynamic. A large, functionally stable, climax community of microbes is maintained in the murine and human gastrointestinal tracts. This open ecosystem exhibits not only regional differences in the composition of its microbiota but also regional differences in the differentiation programs of its epithelial cells and in the spatial distribution of its component immune cells. A key experimental strategy for determining whether “nonpathogenic” microorganisms actively create their own regional habitats in this ecosystem is to define cellular function in germ-free animals and then evaluate the effects of adding single or several microbial species. This review focuses on how gnotobiotics—the study of germ-free animals—has been and needs to be used to examine how the gastrointestinal ecosystem is created and maintained. Areas discussed include the generation of simplified ecosystems by using genetically manipulatable microbes and hosts to determine whether components of the microbiota actively regulate epithelial differentiation to create niches for themselves and for other organisms; the ways in which gnotobiology can help reveal collaborative interactions among the microbiota, epithelium, and mucosal immune system; and the ways in which gnotobiology is and will be useful for identifying host and microbial factors that define the continuum between nonpathogenic and pathogenic. A series of tests of microbial contributions to several pathologic states, using germ-free and ex-germ-free mice, are proposed.

https://mmbr.asm.org/content/mmbr/62/4/1157.full.pdf

Creating and Maintaining the Gastrointestinal Ecosystem: What We Know and Need To Know from Gnotobiology

Infection with Helicobacter pylori is associated with different human gastric diseases. Biochemical studies, in vitro adherence assays, and in vivo animal models revealed that epithelial attachment of H. pylori can be mediated by the blood-group antigen-binding adhesin (BabA) targeting human Lewisb surface epitopes. Studies with transgenic mice expressing the Lewisb epitope have shown that such attachment can alter disease outcome. In the current study, the presence of the babA2 gene encoding the adhesin was investigated in clinical isolates from a German population by using PCR and reverse transcription–PCR. A positive genotype was correlated to allelic variations in the genes encoding VacA and CagA and also to the prevalence of duodenal ulcer, distal gastric adenocarcinoma, mucosa-associated lymphoid tissue lymphoma, and antral gastritis. The presence of babA2 was significantly associated with duodenal ulcer (P = 0.0002) and adenocarcinoma (P = 0.033). In contrast, type 1 strains (vacAs1- and cagA-positive) were associated with only duodenal ulcer (P = 0.004) but not adenocarcinoma (P = 0.235). Genotype presence of babA2, vacAs1, and cagA (“triple-positive” strains) showed a highly significant correlation to the prevalence of ulcer (P = 0.000002) and adenocarcinoma (P = 0.014) and discriminated significantly better between disease outcome than did the current type 1 classification. These results indicate that the babA2 gene is of high clinical relevance and would be a useful marker to identify patients who are at higher risk for specific H. pylori-related diseases.

https://www.pnas.org/content/pnas/96/22/12778.full.pdf

Clinical relevance of the helicobacter pylori gene for blood-group antigen-binding adhesin

The human pathogen Helicobacter pylori is associated with gastritis, peptic ulcer disease, and gastric cancer. The pathogenesis of H. pylori infection in vivo was studied by adapting fresh clinical isolates of bacteria to colonize the stomachs of mice. A gastric pathology resembling human disease was observed in infections with cytotoxin-producing strains but not with noncytotoxic strains. Oral immunization with purified H. pylori antigens protected mice from bacterial infection. This mouse model will allow the development of therapeutic agents and vaccines against H. pylori infection in humans.

https://science.sciencemag.org/content/sci/267/5204/1655.full.pdf

Development of a mouse model of Helicobacter pylori infection that mimics human disease.

Whey, a protein complex derived from milk, is being touted as a functional food with a number of health benefits. The biological components of whey, including lactoferrin, betalactoglobulin, alpha-lactalbumin, glycomacropeptide, and immunoglobulins, demonstrate a range of immune-enhancing properties. In addition, whey has the ability to act as an antioxidant, antihypertensive, antitumor, hypolipidemic, antiviral, antibacterial, and chelating agent. The primary mechanism by which whey is thought to exert its effects is by intracellular conversion of the amino acid cysteine to glutathione, a potent intracellular antioxidant. A number of clinical trials have successfully been performed using whey in the treatment of cancer, HIV, hepatitis B, cardiovascular disease, osteoporosis, and as an antimicrobial agent. Whey protein has also exhibited benefit in the arena of exercise performance and enhancement. (Altern Med Rev 2004;9(2):136-156)

/pdf/therapeutic-applications-of-whey-protein-2nev6ow1qy.pdf

Therapeutic applications of whey protein.

The National Institutes of Health Consensus Development Conference onHelicobacter pyloriin Peptic Ulcer Disease brought together specialists in gastroenterology, surgery, infectious diseases, epidemiology, and pathology, as well as the public to address the following questions: (1) What is the causal relationship ofH pylorito upper gastrointestinal disease? (2) How does one diagnose and eradicateH pyloriinfection? (3) Does eradication ofH pyloriinfection benefit the patient with peptic ulcer disease? (4) What is the relationship betweenH pyloriinfection and gastric malignancy? (5) WhichH pylori—infected patients should be treated? (6) What are the most important questions that must be addressed by future research inH pyloriinfections? Following 1½ days of presentations by experts and discussion by the audience, a consensus panel weighed the evidence and prepared their consensus statement. Among their findings, the consensus panel concluded that (1) ulcer patients withH pyloriinfection require treatment with antimicrobial agents in addition to antisecretory drugs whether on first presentation with the illness or on recurrence; (2) the value of treating of nonulcerative dyspepsia patients withH pyloriinfection remains to be determined; and (3) the interesting relationship betweenH pyloriinfection and gastric cancers requires further exploration. (JAMA. 1994;272:65-69)

Jay H. Hoofnagle

Papers

Helicobacter pylori in Peptic Ulcer Disease