Nightshade Vegetables: A Dietary Trigger for Worsening Inflammatory Bowel Disease and Irritable Bowel Syndrome?

The Solanaceae family of plants, commonly known as Nightshade vegetables or Nightshades, contains a diverse range of crops of over 2000 members with significant culinary, economic, and cultural importance. Familiar edible Nightshades include tomatoes, peppers, eggplants, and white potatoes. Many pharmacologically active compounds used in traditional medicine, including atropine and hyoscyamine, are derived from Nightshades. In addition to these beneficial pharmacologic agents, Nightshade-derived glycoalkaloid compounds, a key defense mechanism against predation, have been shown to disrupt intestinal epithelium and to potentially activate mast cells in the gut mucosa, leading to adverse symptoms in humans. There is a new appreciation that mast cell activation is an allergic inflammatory mechanism contributing both to pain in irritable bowel syndrome (IBS) and to gut inflammation in inflammatory bowel disease (IBD). Given their ubiquity in Western diets and their shared glycoalkaloid active compounds, edible Nightshades are attracting new interest as a potential trigger for worsening gut symptoms in functional and inflammatory gastrointestinal disorders. Here, we review the limited existing literature on the adverse effects of Nightshade consumption, including the effects of Nightshade-derived glycoalkaloids on IBD gut inflammation, and the under-recognized contribution of Nightshades to food allergies and allergic cross-reactivity. We then highlight new evidence on the contributions of mast cell activation to GI disorder pathogenesis, including potential linkages between Nightshade antigens, intestinal mast cells, and GI dysfunction in IBS and IBD.

Should high-fiber diets be recommended for patients with inflammatory bowel disease?

PURPOSE OF REVIEW: Dietary fiber intake in IBD patients has oftentimes generated conflicting data and clinical recommendations. This review aims to unify apparently conflicting lines of evidence regarding dietary fiber intake in IBD patients by highlighting new information from natural history studies and prospective clinical trials. RECENT FINDINGS: IBD patients have lower dietary fiber intake than the general population as well as national guideline recommendations. Patients report short-term benefits from fiber avoidance. Low fiber and low FODMAP diets are associated with lower fecal microbiota abundance and essential nutrient intake. There is emerging evidence suggesting that IBD patients may be able to increase dietary fiber intake with short-term benefit and good tolerability, particularly when fiber is introduced during clinical remission. Current societal recommendations do not favor withholding dietary fiber during long-term IBD management. The long-term impact of increased dietary fiber on IBD clinical outcomes remains unanswered. SUMMARY: Dietary fiber intake is not necessarily contraindicated in IBD patients.

Is Salt at Fault? Dietary Salt Consumption and Inflammatory Bowel Disease.

Epidemiological trends have led to a growing consensus that diet plays a central role in the etiopathogenesis of inflammatory bowel diseases (IBD). A Western diet high in ultra-processed foods has been associated with an increased prevalence of IBD worldwide. Much attention has focused on components of the Western diet, including the high fat content, lack of fiber, added sugars, and use of additives, such as carrageenan and other emulsifiers. Less attention has been paid to the impact of high salt intake, an integral component of ultra-processed foods, which has increased dramatically in the US diet over the past 50 years. We review a growing body of literature linking the rise in dietary salt intake with the epidemiology of IBD, increased consumption of salt as a component of ultra-processed foods, high salt intake and imbalances in immune homeostasis, the effects of a high-salt diet on other inflammatory disorders, salt's impact on animal colitis models, salt as an underrecognized component in diet modification-induced remission of IBD, and directions for future investigation.

Recent studies have shown that high dietary salt intake is proinflammatory and contributes to chronic inflammatory conditions. Combined with investigations demonstrating low-salt exclusive enteral nutrition induced Crohn's remission, salt intake is likely a contributory factor to inflammatory bowel diseases' pathogenesis and severity.

Fatal Venous Gas Embolism During Endoscopic Retrograde Cholangiopancreatography After Simultaneous Deployment of 2 Self-Expandable Metallic Stents.

Gas embolisms are a rare complication of endoscopic retrograde cholangiopancreatography (ERCP). While there have been multiple reports of ERCP-associated air embolisms, only 2 case reports using oral cholangioscopy and CO2 insufflation have been reported in the literature. We present a unique case of a fatal CO2 venous air embolism during ERCP without using cholangioscopy and with no intentional CO2 insufflation of the biliary tree.

As We Drink and Breathe: Adverse Health Effects of Microcystins and Other Harmful Algal Bloom Toxins in the Liver, Gut, Lungs and Beyond.

Freshwater harmful algal blooms (HABs) are increasing in number and severity worldwide. These HABs are chiefly composed of one or more species of cyanobacteria, also known as blue-green algae, such as Microcystis and Anabaena. Numerous HAB cyanobacterial species produce toxins (e.g., microcystin and anatoxin-collectively referred to as HAB toxins) that disrupt ecosystems, impact water and air quality, and deter recreation because they are harmful to both human and animal health. Exposure to these toxins can occur through ingestion, inhalation, or skin contact. Acute health effects of HAB toxins have been well documented and include symptoms such as nausea, vomiting, abdominal pain and diarrhea, headache, fever, and skin rashes. While these adverse effects typically increase with amount, duration, and frequency of exposure, susceptibility to HAB toxins may also be increased by the presence of comorbidities. The emerging science on potential long-term or chronic effects of HAB toxins with a particular emphasis on microcystins, especially in vulnerable populations such as those with pre-existing liver or gastrointestinal disease, is summarized herein. This review suggests additional research is needed to define at-risk populations who may be helped by preventative measures. Furthermore, studies are required to develop a mechanistic understanding of chronic, low-dose exposure to HAB toxins so that appropriate preventative, diagnostic, and therapeutic strategies can be created in a targeted fashion.

Novel Protein Disulfide Isomerase Inhibitor with Anticancer Activity in Multiple Myeloma.

Multiple myeloma cells secrete more disulfide bond-rich proteins than any other mammalian cell. Thus, inhibition of protein disulfide isomerases (PDI) required for protein folding in the endoplasmic reticulum (ER) should increase ER stress beyond repair in this incurable cancer. Here, we report the mechanistically unbiased discovery of a novel PDI-inhibiting compound with antimyeloma activity. We screened a 30,355 small-molecule library using a multilayered multiple myeloma cell-based cytotoxicity assay that modeled disease niche, normal liver, kidney, and bone marrow. CCF642, a bone marrow-sparing compound, exhibited a submicromolar IC50 in 10 of 10 multiple myeloma cell lines. An active biotinylated analog of CCF642 defined binding to the PDI isoenzymes A1, A3, and A4 in MM cells. In vitro, CCF642 inhibited PDI reductase activity about 100-fold more potently than the structurally distinct established inhibitors PACMA 31 and LOC14. Computational modeling suggested a novel covalent binding mode in active-site CGHCK motifs. Remarkably, without any further chemistry optimization, CCF642 displayed potent efficacy in an aggressive syngeneic mouse model of multiple myeloma and prolonged the lifespan of C57BL/KaLwRij mice engrafted with 5TGM1-luc myeloma, an effect comparable to the first-line multiple myeloma therapeutic bortezomib. Consistent with PDI inhibition, CCF642 caused acute ER stress in multiple myeloma cells accompanied by apoptosis-inducing calcium release. Overall, our results provide an illustration of the utility of simple in vivo simulations as part of a drug discovery effort, along with a sound preclinical rationale to develop a new small-molecule therapeutic to treat multiple myeloma. Cancer Res; 76(11); 3340-50. ©2016 AACR.