The gut microbiome and colorectal cancer: a review of bacterial pathogenesis.

Colorectal cancer (CRC) is the third most common newly diagnosed cancer in both men and women in the Unites States. Colonoscopy has become increasingly popular in CRC screening and represents the gold standard for detecting and removing pre-cancerous lesions. Although colonoscopy is considered a relatively safe procedure, it is invasive and bowel preparation can be challenging for patients. As interest in the gut microbiome has expanded, there have been new links established between bacteria and the development of CRC. These developing associations could prove to be a useful adjunct to colonoscopy for CRC screening in the future. This review examines current research evaluating multiple proposed pathogenic microorganisms including sulfidogenic bacteria such as Bilophila wadsworthia, as well as Streptococcus bovis, Helicobacter pylori, Bacteroides fragilis, and Clostridium septicum. This discussion primarily focuses on bacterial pathogenesis, evidence of association with CRC, and the proposed mechanisms of carcinogenesis.

Oral clopidogrel improves cutaneous microvascular function through EDHF-dependent mechanisms in middle-aged humans.

Platelet P2Y12-ADP and COX-1 receptor inhibition with oral clopidogrel (CLO) and low-dose aspirin (ASA), respectively, attenuates reflex-mediated cutaneous vasodilation, but little is known about how these medications affect local vasodilatory signaling. Reactive hyperemia (RH) results in vasodilation that is mediated by sensory nerves and endothelium-derived hyperpolarization factors (EDHF) through large-conductance calcium-activated potassium channels, whereas slow local heating (LH) elicits vasodilation largely through the production of nitric oxide (NO). We hypothesized that CLO and ASA would attenuate locally mediated cutaneous vasodilation assessed by RH and LH (0.5°C/min). In a randomized, cross-over, double-blind placebo-controlled study, nine healthy men and women (56 ± 1 yr) took CLO (75 mg), ASA (81 mg), and placebo for 7 days. Skin blood flow was measured (laser-Doppler flowmetry, LDF) and cutaneous vascular conductance (CVC) was calculated (LDF/mean arterial pressure) and normalized to maximal CVC (%CVCmax: 43°C and 28 mM sodium nitroprusside). RH response parameters, including area under the curve (AUC), total hyperemic response (THR), and the decay constant tau (λ) were calculated. NO-dependent vasodilation during LH was assessed by calculating the difference in %CVCmax between a control site and an NO synthase-inhibited site (10 mM l-NAME: intradermal microdialysis). CLO augmented the AUC and THR (AUCclo = 3,783 ± 342; THRclo = 2,306 ± 266% CVCmax/s) of the RH response compared with ASA (AUCASA = 3,101 ± 325; THRASA = 1,695 ± 197% CVCmax/s) and placebo (AUCPlacebo = 3,000 ± 283; THRPlacebo = 1,675 ± 170% CVCmax/s; all P < 0.0001 vs. CLO). There was no difference in the LH response or calculated NO-dependent vasodilation among treatments (all P > 0.05). Oral CLO treatment augments vasodilation during RH but not LH, suggesting that CLO may improve cutaneous microvascular function.

Aspirin and clopidogrel alter core temperature and skin blood flow during heat stress.

UNLABELLED: Antithrombotic therapy with oral aspirin (ASA) or clopidogrel (CLO) (Plavix; Bristol-Myers Squibb, Bridgewater, NJ) is associated with an attenuated skin vasodilator response and a greater rate of rise in core temperature in healthy, middle-age individuals during passive heating in a water perfused suit. PURPOSE: The present double-blind, crossover study examined the functional consequences of 7 d of low-dose ASA (81 mg·d) versus CLO (75 mg·d) treatment in 14 healthy, middle-age (50-65 yr) men and women during passive heating in air (40 min at 30°C, 40% relative humidity) followed by exercise (60% V˙O2peak). METHODS: Oral temperature (Tor) was measured in the antechamber (23.0°C ± 0.1°C) before entering a warm environmental chamber. After 40 min of rest, subjects cycled on a recumbent cycle ergometer for up to 120 min. Esophageal temperature (Tes) and laser Doppler flux were measured continuously, and the latter was normalized to maximal cutaneous vascular conductance (%CVCmax). RESULTS: Before entry into the environmental chamber there were no differences in Tor among treatments; however, after 40 min of rest in the heat, Tes was significantly higher for ASA and CLO versus placebo (37.2°C ± 0.1°C, 37.3°C ± 0.1°C, vs 37.0°C ± 0.1°C, both P < 0.001), a difference that persisted throughout exercise (P < 0.001 vs placebo). The mean body temperature thresholds for the onset of cutaneous vasodilation were shifted to the right for both ASA and CLO during exercise (P < 0.05). CONCLUSION: ASA and CLO resulted in elevated core temperatures during passive heat stress and shifted the onset of peripheral thermoeffector mechanisms toward higher body temperatures during exercise heat stress.