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Histological staining has long been the gold standard for cancer detection, but it is limited by subjectivity and delayed results. Fourier Transform Infrared Spectroscopy (FTIR) has emerged as a promising technique, offering the advantages of objectivity and real-time analysis. Despite its potential, IR biomarkers developed in different studies are based on varying experimental conditions, including different tissue preparation methods, instrumentation, and patient heterogeneity, which hinder their generalizability and transferability. In this study, tissue spectra from various colorectal cancer cases were systematically collected, and IR biomarkers were developed using the band ratios identified in these spectra. Their ability to differentiate cancer-bearing from non-cancer-bearing tissues was evaluated using a machine learning technique. The results show that the top three biomarkers are b1 (1740/1236), b2 (1740/1162) and b3 (1740/1080). When transferring these biomarkers to a new case (approved under the Ohio State University Institutional Review Board # 2011C0085), b1 effectively differentiates tumor, normal, and margin tissues, while the performance of the b2 and b3 are less satisfactory. This suggests that b1 is more robust and sensitive to key molecular features, whereas b2 and b3 are more likely to be affected by tissue heterogeneity or experimental variations. Combining biomarkers enhances tissue differentiation, but the enhancement plateaus after two to three key biomarkers, as adding more introduces overlapping or redundant information. This study provides a benchmark for future research, with the aim of advancing the clinical translation of noninvasive infrared spectroscopy for intraoperative applications.

Key Points Antibiotic-resistant bacteria, which are a serious threat to the treatment of bacterial diseases, arise as a result of exposure to antibiotics in clinical and agricultural settings. However, antibiotic resistance genes are also naturally present in microbial communities regardless of human influence. Research is needed to understand the emergence and spread of resistance genes among all environments. Antibiotic resistance in bacteria that are associated with wild animals is correlated with the proximity of the animals (and the bacteria) to human populations. Wild animals, and migratory wild birds in particular, are important contributors to the widespread dissemination of antibiotic resistance genes. Microbial communities harbour antibiotic-resistant bacteria regardless of the human use of antibiotics, as evidenced by the presence of novel mechanisms of resistance and phylogenetically divergent resistance genes in unpolluted soil microbial communities. Resistance to antibiotics may be a side effect of the original function of certain gene products, such as efflux pumps. Understanding the function of these gene products in natural microbial communities may uncover new ways of inhibiting the development of resistance in pathogens. The roles of so-called antibiotic resistance genes in natural microbial communities is unknown, although potential roles include antibiotic resistance, metabolic diversification and signal disruption. The fitness conferred by resistance genes to bacteria in their native hosts and habitats needs further study. Future work should focus on standardizing the methods used to acquire data about environmental antibiotic resistance genes and on understanding the many factors affecting the spread of antibiotic resistance genes. Antibiotic resistance seriously threatens our ability to treat infectious diseases. The genes conferring resistance can easily move between organisms, resulting in nearly untreatable diseases. Jo Handelsman and colleagues describe how resistance is spread, the origin of the genes conferring this resistance and the roles they may have in their natural environments. Antibiotic-resistant pathogens are profoundly important to human health, but the environmental reservoirs of resistance determinants are poorly understood. The origins of antibiotic resistance in the environment is relevant to human health because of the increasing importance of zoonotic diseases as well as the need for predicting emerging resistant pathogens. This Review explores the presence and spread of antibiotic resistance in non-agricultural, non-clinical environments and demonstrates the need for more intensive investigation on this subject.

Disturbance of the beneficial gut microbial community is a potential collateral effect of antibiotics, which have many uses in animal agriculture (disease treatment or prevention and feed efficiency improvement). Understanding antibiotic effects on bacterial communities at different intestinal locations is essential to realize the full benefits and consequences of in-feed antibiotics. In this study, we defined the lumenal and mucosal bacterial communities from the small intestine (ileum) and large intestine (cecum and colon) plus feces, and characterized the effects of in-feed antibiotics (chlortetracycline, sulfamethazine and penicillin (ASP250)) on these communities. 16S rRNA gene sequence and metagenomic analyses of bacterial membership and functions revealed dramatic differences between small and large intestinal locations, including enrichment of Firmicutes and phage-encoding genes in the ileum. The large intestinal microbiota encoded numerous genes to degrade plant cell wall components, and these genes were lacking in the ileum. The mucosa-associated ileal microbiota harbored greater bacterial diversity than the lumen but similar membership to the mucosa of the large intestine, suggesting that most gut microbes can associate with the mucosa and might serve as an inoculum for the lumen. The collateral effects on the microbiota of antibiotic-fed animals caused divergence from that of control animals, with notable changes being increases in Escherichia coli populations in the ileum, Lachnobacterium spp. in all gut locations, and resistance genes to antibiotics not administered. Characterizing the differential metabolic capacities and response to perturbation at distinct intestinal locations will inform strategies to improve gut health and food safety.

Pain and inflammation are biologically intertwined responses that warn the body of potential danger. In this issue of the JCI , Defaye, Bradaia, and colleagues identified a functional link between inflammation and pain, demonstrating that inflammation-induced activation of stimulator of IFN genes (STING) in dorsal root ganglia nociceptors reduced pain-like behaviors in a rodent model of inflammatory pain. Utilizing mice with a gain-of-function STING mutation, Defaye, Bradaia, and colleagues identified type I IFN regulation of voltage-gated potassium channels as the mechanism of this pain relief. Further investigation into mechanisms by which proinflammatory pathways can reduce pain may reveal druggable targets and insights into new approaches for treating persistent pain.

Antibiotics have been administered to agricultural animals for disease treatment disease prevention, and growth promotion for over 50 y. The impact of such antibiotic use on the treatment of human diseases is hotly debated. We raised pigs in a highly controlled environment with one portion of the littermates receiving a diet containing performance-enhancing antibiotics [chlortetracycline, sulfamethazine, and penicillin (known as ASP250)] and the other portion receiving the same diet but without the antibiotics. We used phylogenetic, metagenomic, and quantitative PCR-based approaches to address the impact of antibiotics on the swine gut microbiota. Bacterial phylotypes shifted after 14 d of antibiotic treatment with the medicated pigs showing an increase in Proteobacteria (1-11%) compared with nonmedicated pigs at the same time point. This shift was driven by an increase in Escherichia coli populations. Analysis of the metagenomes showed that microbial functional genes relating to energy production and conversion were increased in the antibiotic-fed pigs. The results also indicate that antibiotic resistance genes increased in abundance and diversity in the medicated swine microbiome despite a high background of resistance genes in nonmedicated swine. Some enriched genes, such as aminoglycoside O-phosphotransferases, confer resistance to antibiotics that were not administered in this study, demonstrating the potential for indirect selection of resistance to classes of antibiotics not fed. The collateral effects of feeding subtherapeutic doses of antibiotics to agricultural animals are apparent and must be considered in cost-benefit analyses.

The results of this meta-analysis demonstrate that “study” and GI sample location are the most significant factors in shaping the swine gut microbiota. However, in comparisons of results from different studies, some biological factors may be obscured by technical variation among studies. Nonetheless, there are some bacterial taxa that appear to form a core microbiota within the swine GI tract regardless of country of origin, diet, age, or breed. Thus, these results provide the framework for future studies to manipulate the swine gut microbiota for potential health benefits. The swine gut microbiota encompasses a large and diverse population of bacteria that play a significant role in pig health. As such, a number of recent studies have utilized high-throughput sequencing of the 16S rRNA gene to characterize the composition and structure of the swine gut microbiota, often in response to dietary feed additives. It is important to determine which factors shape the composition of the gut microbiota among multiple studies and if certain bacteria are always present in the gut microbiota of swine, independently of study variables such as country of origin and experimental design. Therefore, we performed a meta-analysis using 20 publically available data sets from high-throughput 16S rRNA gene sequence studies of the swine gut microbiota. Next to the “study” itself, the gastrointestinal (GI) tract section that was sampled had the greatest effect on the composition and structure of the swine gut microbiota ( P = 0.0001). Technical variation among studies, particularly the 16S rRNA gene hypervariable region sequenced, also significantly affected the composition of the swine gut microbiota ( P = 0.0001). Despite this, numerous commonalities were discovered. Among fecal samples, the genera Prevotella , Clostridium , Alloprevotella , and Ruminococcus and the RC9 gut group were found in 99% of all fecal samples. Additionally, Clostridium , Blautia , Lactobacillus , Prevotella , Ruminococcus , Roseburia , the RC9 gut group, and Subdoligranulum were shared by >90% of all GI samples, suggesting a so-called “core” microbiota for commercial swine worldwide. IMPORTANCE The results of this meta-analysis demonstrate that “study” and GI sample location are the most significant factors in shaping the swine gut microbiota. However, in comparisons of results from different studies, some biological factors may be obscured by technical variation among studies. Nonetheless, there are some bacterial taxa that appear to form a core microbiota within the swine GI tract regardless of country of origin, diet, age, or breed. Thus, these results provide the framework for future studies to manipulate the swine gut microbiota for potential health benefits.

Despite the threat posed by antibiotic resistance in infectious bacteria, little is known about the diversity, distribution and origins of resistance genes, particularly among the as yet unculturable environmental bacteria. One potentially rich but largely unstudied environmental reservoir is soil. The complexity of its microbial community coupled with its high density of antibiotic-producing bacteria makes the soil a likely origin for diverse antibiotic resistance determinants. To investigate antibiotic resistance genes among uncultured bacteria in an undisturbed soil environment, we undertook a functional metagenomic analysis of a remote Alaskan soil. We report that this soil is a reservoir for β-lactamases that function in Escherichia coli , including divergent β-lactamases and the first bifunctional β-lactamase. Our findings suggest that even in the absence of selective pressure imposed by anthropogenic activity, the soil microbial community in an unpolluted site harbors unique and ancient β-lactam resistance determinants. Moreover, despite their evolutionary distance from previously known genes, the Alaskan β-lactamases confer resistance on E. coli without manipulating its gene expression machinery, demonstrating the potential for soil resistance genes to compromise human health, if transferred to pathogens.