The intricate connection between diet, microbiota, and cancer: A jigsaw puzzle.

The microbial community has a decisive role in determining our health and disease susceptibility. Presumably, this is closely associated with the complex community network of bacteria, fungi, archaea and viruses that reside our guts. This dynamic ecosystem exists in a symbiotic relationship with its host and plays a fundamental role in the hosts' physiological functions. The microbial community is highly personalized and therefore exhibits a high degree of inter-individual variability, which is dependent on host specifics such as genetic background, physiology and lifestyle. Although the gut microbiota is shaped early on during birth, there are several factors that affect the composition of microbiota during childhood and adulthood. Among them diet appears to be a consistent and prominent one. The metabolic activity of bacteria affects food digestion, absorption, energy production, and immunity. Thus, definition of the microbiota composition and functional profiles in response to a particular diet may lead to critical information on the direct and indirect role/use of the bacterial community during health and disease. In this review, I discuss gut microbiota and its potential link to cancer with specific emphasis on metabolism and diet.

Lymphotoxin ß receptor signaling promotes development of autoimmune pancreatitis.

BACKGROUND & AIMS: Little is known about the pathogenic mechanisms of autoimmune pancreatitis (AIP), an increasingly recognized, immune-mediated form of chronic pancreatitis. Current treatment options are limited and disease relapse is frequent. We investigated factors that contribute to the development of AIP and new therapeutic strategies. METHODS: We used quantitative polymerase chain reaction, immunohistochemical, and enzyme-linked immunosorbent analyses to measure the expression of cytokines and chemokines in tissue and serum samples from patients with and without AIP. We created a mouse model of human AIP by overexpressing lymphotoxin (LT)α and ß specifically in acinar cells (Ela1-LTab mice). RESULTS: Messenger RNA levels of LTα and ß were increased in pancreatic tissues from patients with AIP, compared with controls, and expression of chemokines (CXCL13, CCL19, CCL21, CCL1, and B-cell-activating factor) was increased in pancreatic and serum samples from patients. Up-regulation of these factors was not affected by corticosteroid treatment. Acinar-specific overexpression of LTαß (Ela1-LTαß) in mice led to an autoimmune disorder with various features of AIP. Chronic inflammation developed only in the pancreas but was sufficient to cause systemic autoimmunity. Acinar-specific overexpression of LTαß did not cause autoimmunity in mice without lymphocytes (Ela1-LTab/Rag1(-/-)); moreover, lack of proinflammatory monocytes (Ela1-LTab/Ccr2(-/-)) failed to prevent AIP but prevented early pancreatic tissue damage. Administration of corticosteroids reduced pancreatitis but did not affect production of autoantibodies, such as antipancreatic secretory trypsin inhibitor in Ela1-LTab mice. In contrast, inhibition of LTßR signaling reduced chemokine expression, renal immune-complex deposition, and features of AIP in Ela1-LTab mice. CONCLUSIONS: Overexpression of LTαß specifically in acinar cells of mice causes features of AIP. Reagents that neutralize LTßR ligands might be used to treat patients with AIP.