Endotoxemia, characterized by an excess of circulating bacterial wall lipopolysaccharide, is associated with systemic inflammation and the metabolic syndrome. Placing 8 healthy subjects on a Western-style diet for 1 month induced a 71% increase in plasma levels of endotoxin activity (endotoxemia), whereas a prudent-style diet reduced levels by 31%. The Western-style diet might, therefore, contribute to endotoxemia by causing changes in gastrointestinal barrier function or the composition of the microbiota. Endotoxemia might also develop in individuals with gastrointestinal barrier impairment. Therapeutic reagents that reduce endotoxemia might reduce systemic inflammation in patients with gastrointestinal diseases or metabolic syndrome.

Probiotics are derived from traditional fermented foods, from beneficial commensals or from the environment. They act through diverse mechanisms affecting the composition or function of the commensal microbiota and by altering host epithelial and immunological responses. Certain probiotic interventions have shown promise in selected clinical conditions where aberrant microbiota have been reported, such as atopic dermatitis, necrotising enterocolitis, pouchitis and possibly irritable bowel syndrome. However, no studies have been conducted that can causally link clinical improvements to probiotic-induced microbiota changes. Whether a disease-prone microbiota pattern can be remodelled to a more robust, resilient and disease-free state by probiotic administration remains a key unanswered question. Progress in this area will be facilitated by: optimising strain, dose and product formulations, including protective commensal species; matching these formulations with selectively responsive subpopulations; and identifying ways to manipulate diet to modify bacterial profiles and metabolism.

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Curcumin, a natural compound used as a food additive, has been shown to have anti-inflammatory and antioxidant properties in cell culture and animal studies. A pure curcumin preparation was administered in an open label study to five patients with ulcerative proctitis and five with Crohn's disease. All proctitis patients improved, with reductions in concomitant medications in four, and four of five Crohn's disease patients had lowered CDAI scores and sedimentation rates. This encouraging pilot study suggests the need for double-blind placebo-controlled follow-up studies.KEY WORDS: curcumin; ulcerative proctitis; Crohn's disease; inflammatory bowel disease.Curcumin is a natural compound found in the plant Curcuma longa which is used as a food additive known as turmeric. The major pigment in turmeric is curcumin (chemical name diferuloymethane), which possesses both anti-inflammatory (1, 2) and antioxidant properties (3, 4) Topical application of curcumin inhibits carcinogeninduced DMA adduct formation and the development of skin tumors. Curcumin also strongly inhibits proliferation of HT-29 and HCT-15 human colon cancer cell lines (5). Dietary administration of curcumin suppresses the development of chemically induced cancers. These properties have led to studies of the chemopreventive effects of curcumin which also showed that the agent reduces colonic inflammatory responses (6). The background for such antiinflammatory activity rests in in vitro and animal model studies. We report here our experience with curcumin therapy in 10 patients with inflammatory bowel disease. MATERIALS AND METHODSFive consecutive patients with ulcerative proctitis or proctosigmoiditis who agreed to participate in this study were entered (Table 1) to 54 years, who had complained of proctitis symptoms for 1 to 32 years. All had been previously treated with 5-aminosalicyclic acid (5ASA) compounds by mouth and/or rectum, three had received corticosteroid therapy at some time, and one subject was taking prednisone, 10 mg per day, at study entry.They were treated with 550 mg of curcumin (DFM 100; 99.5% pure 1 ) twice daily for 1 month and then 550 mg three times daily for another month. All had blood taken for hematologic and biochemical analysis and for indexes of inflammation (sedimentation rate and C-reactive protein [CRP]) and had sigmoidoscopies and biopsies both at baseline and 2 months later when the study ended.Symptoms were assessed by a standard questionnaire at the start and conclusion of the study and by a daily symptom dairy. The endoscopic evaluation was not blinded since the investigator was aware of the timing of the procedure, however, the biopsies were obtained and evaluated for the degree of inflammation without knowledge of their timing.Five subjects, three men and two women, with an established diagnosis of Crohn's disease were entered in this pilot study to determine whether the addition of curcumin to existing treatments for Crohn's disease would result in a reduction of inflammation with the ability to reduce other c...

Obesity is associated with chronic, low-grade inflammation, which can disrupt homeostasis within tissue microenvironments. Given the correlation between obesity and relative risk of death from cancer, we investigated whether obesity-associated inflammation promotes metastatic progression. We demonstrate that obesity causes lung neutrophilia in otherwise normal mice, which is further exacerbated by the presence of a primary tumour. The increase in lung neutrophils translates to increased breast cancer metastasis to this site, in a GM-CSF- and IL5-dependent manner. Importantly, weight loss is sufficient to reverse this effect, and reduce serum levels of GM-CSF and IL5 in both mouse models and humans. Our data indicate that special consideration of the obese patient population is critical for effective management of cancer progression.

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Obesity is among the fastest growing diseases worldwide; treatment is inadequate and associated disorders, including gastrointestinal cancers, have high morbidity and mortality. An increased understanding of the mechanisms of obesity-induced carcinogenesis is required to develop methods to prevent or treat these cancers. We review the mechanisms of obesity-associated colorectal, esophageal, gastric, and pancreatic cancers and potential treatment strategies.

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