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(1) Background: Colorectal cancer is one of the leading causes of cancer-related death, while early detection decreases incidence and mortality. Current screening programs involving fecal immunological testing and colonoscopy commonly bring about unnecessary colonoscopies, which adds burden to healthcare systems. The objective of this study was to provide an assessment of the diagnostic performance of an electronic nose serving as a complementary screening tool to improve current screening programs in clinical settings. (2) Methods: We conducted a case–control study that included patients from a medical center with colorectal cancer and non-colorectal cancer controls. We analyzed the composition of volatile organic compounds in their exhaled breath using the electronic nose. We then used machine learning algorithms to develop predictive models and provided the estimated accuracy and reliability of the breath testing. (3) Results: We enrolled 77 patients, with 40 cases and 37 controls. The area under the curve, Kappa coefficient, sensitivity, and specificity of the selected model were 0.87 (95% CI 0.76–0.95), 0.66 (95% CI 0.49–0.83), 0.81, and 0.85. For subjects at an early stage of disease, the sensitivity and specificity were 0.90 and 0.85. Excluding smokers, the sensitivity and specificity were 0.88 and 0.92. (4) Conclusions: This study highlights the promising potential of breath testing using an electronic nose for enabling early detection and reducing unnecessary treatments. However, more independent data for external validation are required to ensure applicability and generalizability. [ABSTRACT FROM AUTHOR]

(1) Background: Colorectal cancer is one of the leading causes of cancer-related death, while early detection decreases incidence and mortality. Current screening programs involving fecal immunological testing and colonoscopy commonly bring about unnecessary colonoscopies, which adds burden to healthcare systems. The objective of this study was to provide an assessment of the diagnostic performance of an electronic nose serving as a complementary screening tool to improve current screening programs in clinical settings. (2) Methods: We conducted a case–control study that included patients from a medical center with colorectal cancer and non-colorectal cancer controls. We analyzed the composition of volatile organic compounds in their exhaled breath using the electronic nose. We then used machine learning algorithms to develop predictive models and provided the estimated accuracy and reliability of the breath testing. (3) Results: We enrolled 77 patients, with 40 cases and 37 controls. The area under the curve, Kappa coefficient, sensitivity, and specificity of the selected model were 0.87 (95% CI 0.76–0.95), 0.66 (95% CI 0.49–0.83), 0.81, and 0.85. For subjects at an early stage of disease, the sensitivity and specificity were 0.90 and 0.85. Excluding smokers, the sensitivity and specificity were 0.88 and 0.92. (4) Conclusions: This study highlights the promising potential of breath testing using an electronic nose for enabling early detection and reducing unnecessary treatments. However, more independent data for external validation are required to ensure applicability and generalizability.

Tuberculosis (TB) affects a third of the global population, and a large population of infected individuals still remain undiagnosed—making the visible burden only the tip of the iceberg. The detection of tuberculosis in close-proximity patients is one of the key priorities for attaining the Sustainable Development Goals (SDG) of TB elimination by 2030. With the current battery of screening tests failing to cover this need, the authors of this paper examined a simple and inexpensive point-of-care breath analyzer (TSI-3000(I)), which is based on detecting the volatile organic compounds that are emitted from infected cells and released in exhaled breath as a screening tool for the detection of TB. A single-center pilot study for assessing the diagnostic accuracy of the point-of-care Tuberculosis Breath Analyzer was conducted, and it was compared against the WHO-recommended TrueNat assay, which is a rapid molecular test and was also treated as the reference standard in this study. Of the 334 enrolled participants with TB signs/symptoms, 42.51% were TrueNat positive for Mycobacterium tuberculosis. The sensitivity of the Tuberculosis Breath Analyzer was found to be 95.7%, with a specificity of 91.3% and a ROC area of 0.935. The test kit showed considerable/significant high sensitivity and specificity as reliability indicators. The performance of the Tuberculosis Breath Analyzer tested was found to be comparable in efficiency to that of the TrueNat assay. A large cohort-based multicentric study is feasibly required to further validate and extrapolate the results of the pilot study.

Background: The potential for exhaled breath to be a valuable diagnostic tool is often overlooked as it can be difficult to imagine how a barely visible sample of breath could hold such a rich source of information about the state of our health. However, technological advances over the last 50 years have enabled us to detect volatile organic compounds (VOCs) present in exhaled breath, and this provides the key to understanding the wealth of information contained within these readily available samples. Summary: VOCs are produced as a by-product of metabolism; hence, changes in the underlying physiological processes will be reflected in the exact composition of VOCs in exhaled breath. It has been shown that characteristic changes occur in the breath VOC profile associated with certain diseases including cancer, which may enable the non-invasive detection of cancer at primary care level for patients with vague symptoms. The use of breath testing as a diagnostic tool has many advantages. It is non-invasive and quick, and the test is widely accepted by patients and clinicians. However, breath samples provide a snapshot of the VOCs present in a particular patient at a given point in time, so this can be heavily influenced by external factors such as diet, smoking, and the environment. These must all be accounted for when attempting to draw conclusions about disease status. This review focuses on the current applications for breath testing in the field of surgery, as well as discussing the challenges encountered with developing a breath test in a clinical environment. The future of breath testing in the surgical setting is also discussed, including the translation of breath research into clinical practice. Key Messages: Analysis of VOCs in exhaled breath can identify the presence of underlying disease including cancer as well as other infectious or inflammatory conditions. Despite the patient factors, environmental factors, storage, and transport considerations that must be accounted for, breath testing demonstrates ideal characteristics for a triage test, being non-invasive, simple, and universally acceptable to patients and clinicians. Many novel biomarkers and diagnostic tests fail to translate into clinical practice because their potential clinical application does not align with the requirements and unmet needs of the healthcare sector. Non-invasive breath testing, however, has the great potential to revolutionise the early detection of diseases, such as cancer, in the surgical setting for patients with vague symptoms. [ABSTRACT FROM AUTHOR]

Aim. To optimize the choice of treatment strategies by physicians and gastroenterologists to improve treatment and prevention of small intestinal bacterial overgrowth (SIBO) in adults.Key points. SIBO is a condition characterized by an increased amount and/or abnormal composition of the microbiota in the small intestine. Clinically, the syndrome is manifested by nonspecific gastroenterological complaints and the development of malabsorption syndrome. Most often, SIBO is associated with various chronic non- infectious diseases (both diseases of the gastrointestinal tract, and the cardiovascular system and the neuromuscular apparatus) and can affect the severity of their symptoms. Specific methods for diagnosing SIBO are the culture method and breath tests. The main approaches to the treatment of SIBO include the elimination of the underlying cause of its occurrence, the use of antibacterial drugs and adherence to dietary recommendations (elemental diet).Conclusion. Small intestinal bacterial overgrowth is common in patients with various diseases, but has non-specific manifestations, so proper diagnosis of this condition is required. SIBO therapy involves prescription of antibacterial agents, the most studied of which is the non-absorbable antibiotic rifaximin-α.

Small intestinal bacterial overgrowth (SIBO) is a clinical entity recognized since ancient times; it represents the consequences of bacterial overgrowth in the small intestine associated with malabsorption. Recently, SIBO as a term has been popularized due to its high prevalence reported in various pathologies since the moment it is indirectly diagnosed with exhaled air tests. In the present article, the results of duodenal/jejunal aspirate culture testing as a reference diagnostic method, as well as the characteristics of the small intestinal microbiota described by culture-dependent and culture-independent techniques in SIBO, and their comparison with exhaled air testing are presented to argue about its overdiagnosis., (Copyright © 2024 Elsevier España, S.L.U. All rights reserved.)

[Display omitted] • The rod-like CaCl 2 @Cu NPs@MIL53(Al)–NH 2 was modified Au screen-printed electrodes. • Ionic liquids were used as electrolytes constructing a planar ammonia sensor. • A novel electrochemical platform for exhaled ammonia analysis was designed. • The prepared sensor has excellent resistance to high humidity and interference. Exhaled gas analysis is an effective and non-invasive method for disease diagnosis. However, due to the complexity of the exhaled gases, this is a challenge for most sensing devices. Herein, CaCl 2 -Cu NPs-MIL53(Al)–NH 2 composites modified with screen-printed electrodes (SPEs) and ionic liquids [BMIM][BF 4 ] were used as electrolytes to construct a novel electrochemical ammonia sensor. CaCl 2 -Cu NPs-MIL53(Al)–NH 2 /SPEs possessed excellent performance, exhibiting good linearity in the range of 0.5–500 ppm with a low limit of detection (0.25 ppm) and a fast response time for 10 ppm ammonia (5.4 s). Most importantly, CaCl 2 -Cu NPs-MIL53(Al)–NH 2 /SPEs showed excellent resistance to high humidity and interference, which is required for exhaled gas analysis. Furthermore, compared to standard spectrophotometry, this method also can provide satisfactory recovery (101.43–103.98 %), suggesting that this sensor is promising for the detection of exhaled gases in the future. [ABSTRACT FROM AUTHOR]

Previous studies have reported volatile organic compounds (VOCs) in the breath as biomarkers of breast cancer. These biomarkers may be derived from cancer-associated fibroblasts, in which oxidative stress degrades polyunsaturated fatty acids to volatile alkanes and methylated alkane derivatives that are excreted in the breath. We evaluated a rapid point-of-care test for breath VOC biomarkers as predictors of breast cancer and abnormal mammograms. We studied 593 women aged⩾18 yr referred to three sites for mammography for a symptomatic breast-related concern (e.g. breast mass, nipple discharge). A rapid point-of-care breath testing system collected and concentrated alveolar breath VOCs on a sorbent trap and analyzed them with gas chromatography and surface acoustic wave detection in <6 min. Breath VOC chromatograms were randomly assigned to a training set or to a validation set. Monte Carlo analysis identified significant breath VOC biomarkers of breast cancer and abnormal mammograms in the training set, and these biomarkers were incorporated into a multivariate algorithm to predict disease in the validation set. Prediction of breast cancer: 50 women had biopsy-proven breast cancer (invasive cancer 41, ductal non-invasive cancer 9) Unsplit data set: breath VOCs identified breast cancer with 83% accuracy (area under curve of receiver operating characteristic), 82% sensitivity and 77.1% specificity. Split data sets: training set breath VOCs identified breast cancer with 80.3% accuracy, 84% sensitivity and 74.3% specificity. Corresponding values in the validation set were 68%% accuracy, 72.4% sensitivity and 61.5% specificity. Prediction of BIRADS 4 and 5 mammograms (versus BIRADS 1, 2 and 3): unsplit data set: breath VOCs identified abnormal mammograms with 76.2% accuracy. Split data sets: breath VOCs identified abnormal mammograms with 74.2% accuracy, 73.3% sensitivity and 60% specificity. Corresponding values in the validation set were 60.5% accuracy, 64.2% sensitivity and 51% specificity. A rapid point-of-care test for breath VOC biomarkers predicted risk of breast cancer and abnormal mammograms in women with breast-related symptoms., (© 2024 IOP Publishing Ltd. All rights, including for text and data mining, AI training, and similar technologies, are reserved.)

Background & Aims: Archaea constitute one of the main 3 domains of the tree of life, distinct from eukaryotes and bacteria. Excessive luminal loads of methanogenic archaea (intestinal methanogen overgrowth [IMO]) have been implicated in the pathophysiology of various diseases, including constipation. To elucidate the phenotypical presentation of IMO, we performed a systematic review and meta-analysis of the prevalence and severity of gastrointestinal symptoms in subjects with IMO as compared with subjects without IMO., Methods: Electronic databases, including OVID MEDLINE and Cochrane Database from inception until September 2023, were systematically searched. Prevalence rates, odds ratios (ORs), standardized mean difference (SMD), and 95% confidence intervals (CIs) of symptoms were calculated., Results: Nineteen studies were included (1293 patients with IMO and 3208 controls). Patients with IMO exhibited various gastrointestinal symptoms, including bloating (78%), constipation (51%), diarrhea (33%), abdominal pain (65%), nausea (30%), and flatulence (56%). Patients with IMO had a significantly higher prevalence of constipation as compared with controls (47% vs 38%; OR, 2.04; 95% CI, 1.48-2.83; P < .0001) along with lower prevalence of diarrhea (37% vs 52%; OR, 0.58; 95% CI, 0.37-0.90; P = .01) and nausea (32% vs 45%; OR, 0.75; 95% CI, 0.60-0.94; P = .01). Patients with IMO had higher severity of constipation (SMD, 0.77; 95% CI, 0.11-1.43; P = .02) and lower severity of diarrhea (SMD, -0.71; 95% CI, -1.39 to -0.03; P = .04). Significant heterogeneity was detected., Conclusion: Patients with IMO exhibit a higher rate and severity of constipation along with lower rate and severity of diarrhea. The distinct phenotype of patients with IMO should be incorporated in patient-reported outcome measures and further correlated with mechanistic microbiome studies., (Copyright © 2024 AGA Institute. All rights reserved.)

Sucrase deficiency has been implicated in chronic abdominal pain. Testing for sucrase deficiency generally involves invasive procedures or lengthy clinical visits, but now noninvasive kits that allow home testing are available to test for sucrase deficiency. In order to assess feasibility and utility of at-home testing, we reviewed our experience in 75 consecutive patients. All patients seen in the abdominal pain clinic had histories obtained in a standardized fashion and all had sucrase breath tests completed at home utilizing a commercially available kit. Testing was completed by 46 patients (61.3%). Tests were abnormal indicating sucrase deficiency in 34.8% of those completing testing. No symptoms were predictive of a positive test although there were trends of an association of an abnormal test with diarrhea and bloating. Our findings suggest that sucrase deficiency occurs frequently enough that more widespread testing and/or an empiric trial of sucrose and starch restriction should be considered. [ABSTRACT FROM AUTHOR]

Small intestinal bacterial overgrowth (SIBO) is characterized by abnormal and excessive amounts of bacteria in the small intestine. Since symptoms and lab tests are non-specific, the diagnosis of SIBO is highly dependent on breath testing. There is a lack of a universally accepted cut-off point for breath testing to diagnose SIBO, and the dilemma of defining “SIBO patients” has made it more difficult to explore the gold standard for SIBO diagnosis. How to validate the gold standard for breath testing without defining “SIBO patients” has become an imperious demand in clinic. Breath-testing datasets from 1071 patients were collected from Xiangya Hospital in the past 3 years and analyzed with an artificial intelligence method using cluster analysis. K-means and DBSCAN algorithms were applied to the dataset after the clustering tendency was confirmed with Hopkins Statistic. Satisfying the clustering effect was evaluated with a Silhouette score, and patterns of each group were described. Advantages of artificial intelligence application in adaptive breath-testing diagnosis criteria with SIBO were discussed from the aspects of high dimensional analysis, and data-driven and regional specific dietary influence. This research work implied a promising application of artificial intelligence for SIBO diagnosis, which would benefit clinical practice and scientific research.

What makes some species successful invaders while others fail, and why some invaders have major impacts in invaded ecosystems are pivotal questions that are attracting major research effort. The increasing availability of high resolution, georeferenced stable isotope landscapes ('isoscapes'), coupled with the commercialization of stable isotope‐enriched tracer molecules and the development of new analytical approaches, is facilitating novel applications of stable isotope techniques in ecology. We can now address ecological questions that were previously intractable.We review and discuss how stable isotope analysis (SIA) can complement fundamental research themes in the study of biological invasions, especially in answering questions relating to the physiological and ecological mechanisms underlying invasion processes and invader impacts.SIA was first used for simply describing the diet of invaders but, more recently, SIA‐informed metrics of population and community trophic structure have been advanced. These approaches now permit the comparison of diets across space and time and provide quantitative tools to compare food webs across different stages of invasion.SIA has also been pivotal in quantifying competition for resources between native and non‐native species (e.g. competition for food, water, or nutrient use). Specific questions related to modes of dispersal (e.g. origin and distance/direction travelled) and mechanisms of establishment can also be addressed using SIA in diverse taxa.An overarching goal is to highlight examples of recent studies that have used SIA in key areas of invasion ecology and use these to synthesize testable predictions where SIA could be applied to future studies. We conclude by highlighting several paths forward and describing how unresolved challenges in quantifying the rates, impacts, and mechanisms underlying invasions could potentially benefit from the use of SIA. [ABSTRACT FROM AUTHOR]

Background: Despite implementation of enhanced recovery after surgery (ERAS) and laparoscopic techniques, postoperative ileus (POI) remains frequent after colorectal surgery, impacting the patient, their recovery and health‐care resources. Presently there are no tests that reliably predict or enable early POI diagnosis. Volatile organic compounds (VC) are products of human and microbiota cellular metabolism and we hypothesised that a detectable alteration occurs in POI. Method: This was a prospective observational study of patients undergoing laparoscopic colorectal resection within an established ERAS programme. Standardized end‐expiratory breath sampling was performed on the morning of surgery and on the first three postoperative mornings. The concentrations of VCs commonly found in intestinal gas were analysed using selected ion flow tube mass spectrometry and GastroCH4ECK®. Feasibility data, bowel preparation, postoperative oral intake, POI and 30‐day morbidity were recorded. Results: Of the 75 potentially eligible patients, 58 (77%) agreed to participate. Per‐protocol breath sampling was successfully completed in 94%. There were no analytical failures. Baseline and postoperative concentrations of VCs were broadly comparable and were not altered by bowel preparation or postoperative oral intake. POI developed in 14 (29%) patients. Preoperative ammonia concentration was higher in patients who developed POI [830 parts per billion (ppb) vs 510 ppb, P = 0.027]. There was an increase in the concentration of acetic acid detected on day 2 in patients who developed POI (99 ppb vs 171 ppb, P = 0.021). Conclusion: Repeated VC breath sampling and analysis is feasible in the perioperative setting. An elevated ammonia concentration on the morning of surgery may be a potential predictor of POI. [ABSTRACT FROM AUTHOR]

We investigated the impact of the ingestion of two green kiwifruit (Actinidia deliciosa var. Hayward) and one Royal Gala apple on breath hydrogen and methane production in humans. Consumption of two green kiwifruit led to no evidence of carbohydrate malabsorption (0/20), whereas consumption of one apple was associated with carbohydrate malabsorption in 6/20 participants (P = .008). There were no significant differences in the area under the curve for hydrogen or methane breath concentrations after consumption of the two fruits. Rates of lactose and fructose breath tests in this cohort were within expected parameters. Green kiwifruit are not associated with clinically significant carbohydrate malabsorption compared with apples in this pilot study. [ABSTRACT FROM AUTHOR]

During fasting, animals rely on a mixture of fats, carbohydrates, and proteins that are derived solely from endogenous sources. The relative contributions of these metabolic fuels chiefly depend on the duration of the fast, but other factors including previous diet, environmental temperature, and activity level can modulate the fuel mixture. It has long been held that endogenous proteins are spared from catabolism until the final stages of prolonged fasting and contribute a significant proportion of energy once the other metabolic fuels have been depleted. However, evidence is mounting that protein is catabolized supplemental to fat metabolism under some circumstances. This has been shown in migratory birds that exhibit dramatic reductions in lean mass during flights. One hypothesis to explain this seemingly maladaptive metabolic strategy is that the catabolism and oxidation of protein in situ yields five times more metabolic water than that generated through fat oxidation alone. Recent support for this hypothesis is that birds benefit from such a strategy due to their uricotelic nature. However, it remains unclear whether ureotelic mammals would also employ this strategy. Here we test the protein-for-water hypothesis in resting laboratory mice subjected to water deprivation during fasting while we tracked rates of protein and lipid catabolism using endogenously incorporated 13C-leucine and 13C-palmitic acid. We found no differences in instantaneous leucine oxidation; however, cumulative differences in instantaneous leucine oxidation ultimately resulted in a higher total leucine oxidation after 72 h of fasting in water-deprived animals. We also found that lipid oxidation was 8% higher in the hydrated mice, but the difference was not significant presumably because of a concomitant reduction in metabolic rates of the water-deprived mice. Our results indicate that mammals do increase rates of protein catabolism during dehydration but to a lesser degree than birds. The ability of mammals to produce highly concentrated urine and their lower inherent rates of protein turnover apparently preclude mammals from taking full advantage of the protein-for-water strategy during fasting under dehydrating conditions. [ABSTRACT FROM AUTHOR]

The risk of food limitation and, ultimately, starvation dates back to the dawn of heterotrophy in animals, yet starvation remains a major factor in the regulation of modern animal populations. Researchers studying starvation more than a century ago suggested that animals subjected to sublethal periods of food limitation are somehow more tolerant of subsequent starvation events. This possibility has received little attention over the past decades, yet it is highly relevant to modern science for two reasons. First, animals in natural populations are likely to be exposed to bouts of food limitation once or more before they face prolonged starvation, during which the risk of mortality becomes imminent. Second, our current approach to studying starvation physiology in the laboratory focuses on nourished animals with no previous exposure to nutritional stress. We examined the relationship between previous exposure to food limitation and potentially adaptive physiological responses to starvation in adult rats and found several significant differences. On two occasions, rats were fasted until they lost 20% of their body mass maintained lower body temperatures, and had presumably lower energy requirements when subjected to prolonged starvation than their naive cohort that never experienced food limitation. These rats that were trained in starvation also had lower plasma glucose set -points and reduced their reliance on endogenous lipid oxidation. These findings underscore (1) the need for biologists to revisit the classic hypothesis that animals can become habituated to starvation, using a modern set of research tools; and (2) the need to design controlled experiments of starvation physiology that more closely resemble the dynamic nature of food availability. [ABSTRACT FROM AUTHOR]

Objectives: Small intestinal bacterial overgrowth (SIBO) is considered a frequent cause of abdominal symptoms in patients with surgically altered intestinal anatomy or dysmotility conditions and is recognized as a contributing factor in the exacerbation of irritable bowel syndrome symptoms. Diagnostic testing can be used to detect the condition.Methods: The study group comprised patients who had breath hydrogen and methane lactulose challenge testing. All of the patients were treated with antibiotic regimens that have shown benefit for SIBO. The lactulose challenge was administered orally at 15 g. Hydrogen and methane in expired air were measured and hydrogen values were recorded as the hydrogen plus twice the methane result. Breath tests were analyzed for positivity based on single and multiple criteria of fasting baseline elevation, early rise, and second peak hydrogen rise. Global improvement of gastrointestinal symptoms was assessed by telephone contact or record review.Results: One hundred participants (78 women) were included in the analysis. The mean age was 51 years. A total of 15% of participants did not meet any criteria on breath testing for SIBO; 73% had a fasting baseline elevation >10 ppm; and 19% had an increase of >20 ppm above baseline in the first 20 minutes, 48% had a 20-ppm increase in the first 60 minutes, and 32% had a second increase, reflecting a colon peak. Overall, 74% responded to a course of antibiotics, determined by reported improvement in more than half of the symptoms within 3 months. In total, 67% (10/15) of the subjects who tested negative for SIBO, by all criteria, had a favorable response to antibiotics. Among those with positive hydrogen increases, 76.3% with 1 criterion responded, 66.7% with 2 criteria responded, 84.6% with 3 responded, and 76.9% with 4 responded. After antibiotic treatment, 88.7% (47/53) of those who had diarrhea reported improvement, 63.3% (19/30) with constipation reported improvement, and 74.3% (52/70) with baseline bloating experienced improvement. Sixty-five of the 82 patients with pain or discomfort reported improvement (79.3%). Of those treated with a rifaximin regimen, 74.2% (49/66) reported a response to treatment. Twenty of 28 (71.4%) treated with amoxicillin/clavulanate experienced a clinical response.Conclusions: These data suggest that the response to antibiotic therapy in patients with suspected SIBO is not predicted by carbohydrate SIBO testing results and bring into question the value of such testing. [ABSTRACT FROM AUTHOR]

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Objective The objective of this study was to investigate changes in volatile organic compounds ( VOCs) in exhaled breath in overweight/obese children compared with their lean counterparts. Study design Single exhaled breath was collected and analyzed per protocol using selective ion flow tube mass spectrometry ( SIFT-MS). Results Sixty overweight/obese children and 55 lean controls were included. Compared with the lean group, the obese group was significantly older (14.1 ± 2.8 vs. 12.1 ± 3.0 years), taller (164.8 ± 10.9 vs. 153.3 ± 17.1 cm) and more likely to be Caucasian (60% vs. 35.2%); P < 0.05 for all. A comparison of the SIFT-MS results of the obese group with the lean group revealed differences in concentration of more than 50 compounds. A panel of four VOCs can identify the presence of overweight/obesity with excellent accuracy. Further analysis revealed that breath isoprene, 1-decene, 1-octene, ammonia and hydrogen sulfide were significantly higher in the obese group compared with the lean group ( P value < 0.01 for all). Conclusion Obese children have a unique pattern of exhaled VOCs. Changes in VOCs observed in this study may help to gain insight into pathophysiological processes and pathways leading to the development of childhood obesity. [ABSTRACT FROM AUTHOR]

Due to various biochemical fractionation processes during lipid synthesis, the lipid molecules in the body contain substantially lower concentrations of 13 C than the nonlipid molecules. Because of the isotopic differences between these two endogenous nutrient pools, any shift toward nonlipid fuel oxidation would be expected to increase in the δ 13 C of the exhaled breath. Interestingly, the possibility of whether or not an exercise-induced change actually occurs has been debated in literature for over two decades and researchers have still not reached a consensus. We measured ventilatory and metabolic variables before, during, and after exercise in forty-eight adults (n = 25 females, n = 23 males; 20.1 ± 1.9 years) assigned to either a resting treatment or one of three exercising treatments where they maintained a heart rate of 130, 150, or 170 bpm for 56 min. We found that the mean metabolic rates of the exercising groups increased 4.4-fold, 6.1-fold, and 7.7-fold above resting values, respectively. Exercise caused small increases in respiratory exchange ratios (e.g., from 0.83 ± 0.08 to 0.86 ± 0.10) indicative of increased carbohydrate oxidation, but these changes were too variable to be reliably correlated with exercise intensity. In contrast, the δ 13 C of the exhaled breath increased by 0.62 ± 0.19‰, 1.14 ± 0.29‰, and 1.79 ± 0.50‰, respectively, for the three groups and was significantly correlated with the intensity of exercise. We also show that the isotopic difference of the lipid and nonlipids of the body is similar (~ 2.7‰) even when consuming bulk diets that are isotopically distinct (> 8‰). If not corrected for, these exercise-induced changes in δ 13 C of the breath would be sufficiently large to skew the results of studies investigating the oxidative fates of exogenous nutritional supplements. [ABSTRACT FROM AUTHOR]