Gut anaerobes protect against pathogen invasion: Intestinal infections are a common problem for young animals. One explanation is that the protective gut microbiota is not fully established in infants. How the microbiota might protect against pathogens is unclear. Kim et al. found that members of the group of strictly anaerobic, spore-forming bacteria known as clostridia protect neonatal mice against diarrhea-causing pathogens. The protective effect is enhanced by giving mice the metabolite succinate in drinking water. Succinate favors colonization of the neonatal gut by cluster IV and XIVa clostridia and concomitantly excludes Salmonella typhimurium. Science , this issue p. 315

A fluorescently labeled peptide enables first-in-human targeted endoscopic imaging of esophageal neoplasia.

Fourier transform infrared (FTIR) spectroscopy provides a unique molecular fingerprint of tissue from endogenous sources of light absorption; however, specific molecular components of the overall FTIR signature of precancer have not been characterized. In attenuated total reflectance mode, infrared light penetrates only a few microns of the tissue surface, and the influence of water on the spectra can be minimized, allowing for the analyses of the molecular composition of tissues. Here, spectra were collected from 98 excised specimens of the distal esophagus, including 38 squamous, 38 intestinal metaplasia (Barrett's), and 22 gastric, obtained endoscopically from 32 patients. We show that DNA, protein, glycogen, and glycoprotein comprise the principal sources of infrared absorption in the 950- to 1,800-cm ⁻¹ regime. The concentrations of these biomolecules can be quantified by using a partial least-squares fit and used to classify disease states with high sensitivity, specificity, and accuracy. Moreover, use of FTIR to detect premalignant (dysplastic) mucosa results in a sensitivity, specificity, positive predictive value, and total accuracy of 92%, 80%, 92%, and 89%, respectively, and leads to a better interobserver agreement between two gastrointestinal pathologists for dysplasia (κ = 0.72) versus histology alone (κ = 0.52). Here, we demonstrate that the concentration of specific biomolecules can be determined from the FTIR spectra collected in attenuated total reflectance mode and can be used for predicting the underlying histopathology, which will contribute to the early detection and rapid staging of many diseases.

Molecular imaging is an emerging strategy for in vivo visualization of cancer over time based on biological mechanisms of disease activity. Optical imaging methods offer a number of advantages for real-time cancer detection, particularly in the epithelium of hollow organs and ducts, by using a broad spectral range of light that spans from visible to near-infrared. Targeted ligands are being developed for improved molecular specificity. These platforms include small molecule, peptide, affibody, activatable probes, lectin, and antibody. Fluorescence labeling is used to provide high image contrast. This emerging methodology is clinically useful for early cancer detection by identifying and localizing suspicious lesions that may not otherwise be seen and serves as a guide for tissue biopsy and surgical resection. Visualizing molecular expression patterns may also be useful to determine the best choice of therapy and to monitor efficacy. A number of these imaging agents are overcoming key challenges for clinical translation and are being validated in vivo for a wide range of human cancers.

Cancer is one of the major causes of mortality and morbidity in our healthcare system. Molecular imaging is an emerging methodology for the early detection of cancer, guidance of therapy, and monitoring of response. The development of new instruments and exogenous molecular probes that can be labeled for multi-modality imaging is critical to this process. Today, molecular imaging is at a crossroad, and new targeted imaging agents are expected to broadly expand our ability to detect and manage cancer. This integrated imaging strategy will permit clinicians to not only localize lesions within the body but also to manage their therapy by visualizing the expression and activity of specific molecules. This information is expected to have a major impact on drug development and understanding of basic cancer biology. At this time, a number of molecular probes have been developed by conjugating various labels to affinity ligands for targeting in different imaging modalities. This review will describe the current status of exogenous molecular probes for optical, scintigraphic, MRI and ultrasound imaging platforms. Furthermore, we will also shed light on how these techniques can be used synergistically in multi-modal platforms and how these techniques are being employed in current research.

Background & Aims Dysplasia is a premalignant condition in Barrett's esophagus that is difficult to detect on endoscopy because of its flat architecture and patchy distribution. Peptides are promising for use as novel molecular probes that identify cell surface targets unique to disease and can be fluorescence-labeled for detection. We aim to select and validate an affinity peptide that binds to esophageal dysplasia for future clinical studies. Methods Peptide selection was performed using phage display by removing nonspecific binders using Q-hTERT (intestinal metaplasia) cells and achieving specific binding against OE33 (esophageal adenocarcinoma) cells. Selective binding was confirmed on bound phage counts, enzyme-linked immunosorbent assay (ELISA), flow cytometry, competitive inhibition, and fluorescence microscopy. On stereomicroscopy, specific peptide binding to dysplasia on endoscopically resected specimens was assessed by rigorous registration of fluorescence intensity to histology in 1-mm intervals. Results The peptide sequence SNFYMPL was selected and showed preferential binding to target cells. Reduced binding was observed on competition with unlabeled peptide in a dose-dependent manner, an affinity of K_d = 164 nmol/L was measured, and peptide binding to the surface of OE33 cells was validated on fluorescence microscopy. On esophageal specimens (n = 12), the fluorescence intensity (mean ± SEM) in 1-mm intervals classified histologically as squamous (n = 145), intestinal metaplasia (n = 83), dysplasia (n = 61), and gastric mucosa (n = 69) was 46.5±1.6, 62.3±5.8, 100.0±9.0, and 42.4 ± 3.0 arb units, respectively. Conclusions The peptide sequence SNFYMPL binds specifically to dysplasia in Barrett's esophagus and can be fluorescence labeled to target premalignant mucosa on imaging.