Our understanding of the microbial involvement in inflammatory bowel disease(IBD) pathogenesis has increased exponentially over the past decade. The development of newer molecular tools for the global assessment of the gut microbiome and the identification of nucleotide-binding oligomerization domain-containing protein 2 in 2001 and other susceptibility genes for Crohn’s disease in particular has led to better understanding of the aetiopathogenesis of IBD. The microbial studies have elaborated the normal composition of the gut microbiome and its perturbations in the setting of IBD. This altered microbiome or 'dysbiosis' is a key player in the protracted course of inflammation in IBD. Numerous genome-wide association studies have identified further genes involved in gastrointestinal innate immunity(including polymorphisms in genes involved in autophagy: ATG16L1 and IGRM), which have helped elucidate the relationship of the local innate immunity with the adjacent luminal bacteria. These developments have also spurred the search for specific pathogens which may have a role in the metamorphosis of the gut microbiome from a symbiotic entity to a putative pathogenic one. Here we review advances in our understanding of microbial involvement in IBD pathogenesis over the past 10 years and offer insight into how this will shape our therapeutic management of the disease in the coming years.
Because reactive oxygen species have been implicated as mediators of inflammatory bowel disease (IBD), we evaluated the potential preventive and therapeutic effects of two dietary antioxidants, glutathione (GSH) and coenzyme Q10 (CoQ10) on dextran sulfate sodium (DSS)-induced colitis in mice. Fifty female 8-wk old Swiss-Webster mice were randomly assigned to 4 groups for a pre-treatment "prevention" study: (1) GSH (1% of diet); (2) CoQ10 (200 mg/kg/d); (3) DSS only (3% of drinking water); (4) control (no treatment). The mice in groups 1 and 2 were fed with GSH or CoQ10 for 21 wks, and the mice in groups 1, 2 and 3 were provided DSS from wk 7 for 4 cycles (1 cycle = 1 wk DSS followed by 2-wk water). Another 50 mice were randomly assigned to 4 groups for a 21-wk "treatment" study where the mice in groups 1, 2, and 3 were administered DSS for 6 cycles (18 wks) to induce colitis. GSH and CoQ10 were added from wk 7 until the completion of the protocol. Loose stools and hemocult positivity were modestly but significantly reduced with GSH or CoQ10 at several periods during the intervention in both the prevention and treatment studies. In contrast, histological evaluation revealed increases in colonic dysplasia and ulceration with GSH or CoQ10. Thus, in this mouse model, GSH and CoQ10 appear to have a beneficial effect on acute signs of IBD, but may have an adverse impact on the chronic pathophysiology of the disease. Further studies using additional animal models are required to determine whether GSH or CoQ10 provide a favorable or unfavorable benefit:risk ratio in the prevention or treatment of IBD.
The Walnut Pest Management Alliance (PMA) for a tenth year continued work to reduce pesticide inputs in California walnuts and demonstrate and increase implementation of pest management strategies based on various formulations of pheromone mating disruption (PMD). Three long-term, area-wide projects continued in 2008 with aerosol pheromone puffers for codling moth (CM) control and three additional sites and an expansion area were created. The majority of the PMD acreage in this project in 2008 did not need supplemental insecticides to control CM, but some blocks did need treatments to control walnut husk fly and navel orangeworm which are not affected by the pheromone program. Several years of using PMD over a large area demonstrate the benefits of this system which include reduced crop damage, reduced CM populations which can be managed using fewer insecticide sprays, reduction of broad spectrum insecticides and a move to softer insecticides to supplement PMD. Data collected from the same locations over several years allows measurement of these reductions. The trial locations are independent and the results are not meant to be compared to each other. Monitoring data from several of the puffer sites was compared to a non-pheromone treated orchard and the resulting graph (Figure 1) was shared regionally. The success of this program depends on the inputs from many collaborators including pest control advisors (PCAs), UCCE Farm Advisors, Suterra LLC, Trece Inc, USDA-ARS, Ca. Dept. of Pesticide Regulation, UC IPM, Walnut Marketing Board, Walnut Entomology Workgroup, growers, and several field assistants. The project is supported by grants from: • Walnut Marketing Board, $23,000 • Western IPM, $55,000 • USDA areawide project, $49,000 • UC IPM Demonstrations, $10,000 OBJECTIVES 1. Validate pheromone application technology required for control of codling moth with an emphasis on “area-wide” control over multiple years. Continue using aerosol puffers at sites in San Joaquin, Glenn, and Butte Counties and expand acreage of SJ site to take advantage of area-wide CM suppression. 2. Create new sites where growers have shown interest in Yolo, and Tehama Counties to increase local visibility and experience with the pheromone puffers. 3. Demonstrate the use of monitoring CM to watch for population increases and to determine spray timings. Monitor damage to the crop with in-season surveys of nuts in the canopy. Over time, the need for supplemental sprays should be decreased and eliminated with CM population reductions.
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