Associations Between Health Behaviors, Gastrointestinal Symptoms, and Gut Microbiota in a Cross-Sectional Sample of Cancer Survivors: Secondary Analysis from the Chemo-Gut Study.

BACKGROUND: Health behaviors, such as diet and exercise, are actions individuals take that can potentially impact gastrointestinal (GI) symptoms and the gut microbiota. Little is known about how health behaviors impact GI symptoms and the gut microbiota after anti-cancer therapies. METHODS: This is a secondary analysis of a cross-sectional study that investigated relationships between GI symptoms, gut microbiota, and patient-reported outcomes in adult cancer survivors. Gut microbiota was assessed from stool samples using 16 S rRNA gene sequencing. GI symptoms and health behaviors were measured via self-report. Descriptive statistics, multiple regression, and correlation analyses are reported. RESULTS: A total of 334 cancer survivors participated, and a subsample of 17 provided stool samples. Most survivors rated their diet as moderately healthy (55.7%) and reported engaging in low intensity exercise (53.9%) for ≤5 h/week (69.1%). Antibiotic use was associated with more belly pain, constipation, and diarrhea (P < .05). Survivors consuming a healthier diet had fewer symptoms of belly pain (P = .03), gas/bloating (P = .01), while higher protein consumption was associated with less belly pain (P = .03). Better diet health was positively correlated with Lachnospiraceae abundance, and negatively with Bacteroides abundance (P < .05). Greater exercise frequency positively correlated with abundance of Lachnospiraceae, Faecalibacterium, Bacteroides, Anaerostipes, Alistipes, and Subdoligranulum (P < .05). CONCLUSION: Results provide evidence for associations between antibiotic use, probiotic use, dietary health behaviors, and GI symptoms. Diet and exercise behaviors are related to certain types of bacteria, but the direction of causality is unknown. Dietary-based interventions may be optimally suited to address survivors' GI symptoms by influencing the gut microbiota. Larger trials are needed.

The Chemo-Gut Study: A Cross-Sectional Survey Exploring Physical, Mental, and Gastrointestinal Health Outcomes in Cancer Survivors.

Background: Cancer treatments, such as chemotherapy, may adversely affect gastrointestinal (GI), physical and mental health in survivors of cancer. Objective: This study investigated associations between GI, mental and physical health outcomes, and cancer treatment-related variables, such as chemotherapy, in adult cancer survivors. Methods: A one-time cross-sectional survey with patient-reported outcomes was used. Cancer survivors (N = 317) aged ≥18 years, living in Canada, who completed cancer treatments were included. Descriptive statistics, correlation, and linear regression analyses are reported. Results: Mean age at diagnosis was 40.90 ± 15.40 years. Most survivors received chemotherapy (86.1%). Persistent GI symptoms include constipation (53.6%), diarrhea (50.5%), and bloating/pain (54.9%). Mean GI symptom duration was 30.53 ± 33.42 months. Severity of GI symptom interference was moderate to extreme for 51.9% of survivors. Compared to normative values of 50 in healthy people, survivors scored poorer for mental health (M = 42.72 ± 8.16) and physical health (M = 45.55 ± 7.93), and reported more belly pain (M = 56.10 ± 8.58), constipation (M = 54.38 ± 6.81), diarrhea (M = 55.69 ± 6.77), and gas/bloating (M = 56.08 ± 8.12). Greater GI symptom severity was associated with poorer mental and physical health (P < .01). Chemotherapy was associated with increased belly pain (B = 4.83, SE = 1.65, P < .01) and gas/bloating (B = 3.06, SE = 1.45, P = .04). Conclusion: We provide novel evidence that many cancer survivors experience chronic, moderate to severe GI symptoms lasting for years after cancer treatment, which are associated with worse mental and physical health. Chemotherapy is associated with specific GI symptoms. Integrative therapies are needed to address GI symptoms in cancer survivors.

Exercise and Prebiotic Fiber Provide Gut Microbiota-Driven Benefit in a Survivor to Germ-Free Mouse Translational Model of Breast Cancer.

The gut microbiota plays a role in shaping overall host health and response to several cancer treatments. Factors, such as diet, exercise, and chemotherapy, can alter the gut microbiota. In the present study, the Alberta Cancer Exercise (ACE) program was investigated as a strategy to favorably modify the gut microbiota of breast cancer survivors who had received chemotherapy. Subsequently, the ability of post-exercise gut microbiota, alone or with prebiotic fiber supplementation, to influence breast cancer outcomes was interrogated using fecal microbiota transplant (FMT) in germ-free mice. While cancer survivors experienced little gut microbial change following ACE, in the mice, tumor volume trended consistently lower over time in mice colonized with post-exercise compared to pre-exercise microbiota with significant differences on days 16 and 22. Beta diversity analysis revealed that EO771 breast tumor cell injection and Paclitaxel chemotherapy altered the gut microbial communities in mice. Enrichment of potentially protective microbes was found in post-exercise microbiota groups. Tumors of mice colonized with post-exercise microbiota exhibited more favorable cytokine profiles, including decreased vascular endothelial growth factor (VEGF) levels. Beneficial microbial and molecular outcomes were augmented with prebiotic supplementation. Exercise and prebiotic fiber demonstrated adjuvant action, potentially via an enhanced anti-tumor immune response modulated by advantageous gut microbial shifts.

The Chemo-Gut Pilot Study: Associations between Gut Microbiota, Gastrointestinal Symptoms, and Psychosocial Health Outcomes in a Cross-Sectional Sample of Young Adult Cancer Survivors.

Chemotherapy adversely affects the gut microbiota, inducing dysbiosis, and negatively impacts gastrointestinal (GI) and psychosocial health during treatment, but little is known about the long-term effects or how these factors are related. Methods: This cross-sectional pilot study investigated the effects of chemotherapy on the gut microbiota, GI symptoms, and psychosocial outcomes in cancer survivors aged 18−39 years old, compared to healthy controls. Gut microbial diversity and composition were assessed from stool samples using 16S rRNA gene sequencing. Results: Survivors (n = 17) and healthy controls (n = 18) participated. Mean age at diagnosis was 31 years (±5.3). Mean time off treatment was 16.9 months (±16.4). Survivors had more severe GI symptoms, poorer psychosocial health, and increased relative abundance of Selenomondales, Veilloneliaceae, and Intestinibacter. In survivors, Lachnospiraceae, Ruminococcaceae and Intestinibacter correlated with psychosocial symptoms, while diarrhea correlated positively with Lachnospiraceae. Results are statistically significant. Survivors ≤6 months post-treatment had lower alpha diversity than survivors >6 months post-treatment (p = 0.04) and controls (p = 0.19). Conclusion: This small exploratory study demonstrates potential long-term gut microbial dysbiosis in cancer survivors, which may be associated with psychosocial symptoms. Larger trials concurrently and longitudinally examining gut microbiota, GI symptoms, and psychosocial outcomes are needed.

The Use of Prebiotic and Probiotic Interventions for Treating Gastrointestinal and Psychosocial Health Symptoms in Cancer Patients and Survivors: A Systematic Review.

BACKGROUND: Cancer treatments can cause significant gastrointestinal (GI) health issues, and negatively affect patient's psychosocial health and quality of life (QOL). Novel, integrative strategies using prebiotics and probiotics have been explored for treating adverse cancer treatment-related side effects. We evaluated the current literature for interventions using prebiotics or probiotics specifically to treat GI and psychosocial health issues in cancer patients and survivors. METHODS: Five databases (PubMed, MEDLINE (Ovid), CINHAL, PsychINFO, Web of Science) were searched for studies with prebiotic or probiotic interventions where GI and/or psychosocial health outcomes were measured in adult cancer patients and survivors, and published before September 12th 2021. RESULTS: Twelve studies (N = 974 participants) meeting the inclusion criteria were identified (randomized controlled trials [n = 10], single-group pre-post studies [n = 2]). Ten studies were conducted with patients on active cancer treatment, and 2 studies treated patients after anti-cancer therapies. Three studies used prebiotics, 7 studies used probiotics, and 2 studies used a combination therapy. The most commonly used probiotic strains were from the Lactobacillus genus. There was minimal evidence for prebiotics to improve GI or psychosocial health. Probiotics were associated with significant improvements in abdominal pain (n = 2), gas/bloating (n = 2), and especially diarrhea (n = 5), and with improvements in anxiety (n = 1), depression (n = 1), fatigue (n = 1), and QOL (n = 2). CONCLUSIONS: Studies specifically examining effects of prebiotics and probiotics on GI and psychosocial health outcomes are scarce. Probiotic intervention may improve some GI symptoms in cancer patients, and QOL in survivors. Controlled trials that consistently include GI and psychosocial health outcomes are needed.

Dietary patterns, food groups and nutrients in Crohn's disease: associations with gut and systemic inflammation.

This study examined associations between dietary intake and gut and systemic inflammation assessed by fecal calprotectin ≤ or > 100 µg/mg (FCP), C-reactive protein ≤ or > 5 mg/L (CRP) and serum cytokine profiles in Crohn's disease (CD) patients in clinical remission. A 3-month observational study was conducted at the University of Calgary in Calgary, Alberta, Canada between 2016 and 2018 in 66 outpatients with CD in clinical remission. FCP was obtained from stool samples at baseline and 3-months and serum CRP and serum cytokines were assessed at 3-months only (n = 41). Dietary intakes were collected using 3-day food records at baseline and 3-months and categorized as: PREDIMED Mediterranean diet scores (pMDS) total and individual components, the dietary inflammatory index (DII), food groups, and common micro- and macro-nutrients. Statistical models were developed to identify relationships between dietary factors and FCP, CRP and cytokine levels. Daily intake of leafy green vegetables was associated with FCP ≤ 100 µg/mg (p < 0.05). Increasing omega 6:3 ratio was associated with CRP ≤ 5 mg/L (p = 0.02). Different cytokines were significantly associated with various dietary variables. Future studies in patients with greater disease activity should be undertaken to explore these relationships.

Influence of iron manipulation on hypoxic pulmonary vasoconstriction and pulmonary reactivity during ascent and acclimatization to 5050 m.

KEY POINTS: Iron acts as a cofactor in the stabilization of the hypoxic-inducible factor family, and plays an influential role in the modulation of hypoxic pulmonary vasoconstriction. It is uncertain whether iron regulation is altered in lowlanders during either (1) ascent to high altitude, or (2) following partial acclimatization, when compared to high-altitude adapted Sherpa. During ascent to 5050 m, the rise in pulmonary artery systolic pressure (PASP) was blunted in Sherpa, compared to lowlanders; however, upon arrival to 5050 m, PASP levels were comparable in both groups, but the reduction in iron bioavailability was more prevalent in lowlanders compared to Sherpa. Following partial acclimatization to 5050 m, there were differential influences of iron status manipulation (via iron infusion or chelation) at rest and during exercise between lowlanders and Sherpa on the pulmonary vasculature. ABSTRACT: To examine the adaptational role of iron bioavailability on the pulmonary vascular responses to acute and chronic hypobaric hypoxia, the haematological and cardiopulmonary profile of lowlanders and Sherpa were determined during: (1) a 9-day ascent to 5050 m (20 lowlanders; 12 Sherpa), and (2) following partial acclimatization (11 ± 4 days) to 5050 m (18 lowlanders; 20 Sherpa), where both groups received an i.v. infusion of either iron (iron (iii)-hydroxide sucrose) or an iron chelator (desferrioxamine). During ascent, there were reductions in iron status in both lowlanders and Sherpa; however, Sherpa appeared to demonstrate a more efficient capacity to mobilize stored iron, compared to lowlanders, when expressed as a Δhepcidin per unit change in either body iron or the soluble transferrin receptor index, between 3400-5050 m (P = 0.016 and P = 0.029, respectively). The rise in pulmonary artery systolic pressure (PASP) was blunted in Sherpa, compared to lowlanders during ascent; however, PASP was comparable in both groups upon arrival to 5050 m. Following partial acclimatization, despite Sherpa demonstrating a blunted hypoxic ventilatory response and greater resting hypoxaemia, they had similar hypoxic pulmonary vasoconstriction when compared to lowlanders at rest. Iron-infusion attenuated PASP in both groups at rest (P = 0.005), while chelation did not exaggerate PASP in either group at rest or during exaggerated hypoxaemia ( PIO2  = 67 mmHg). During exercise at 25% peak wattage, PASP was only consistently elevated in Sherpa, which persisted following both iron infusion or chelation. These findings provide new evidence on the complex interplay of iron regulation on pulmonary vascular regulation during acclimatization and adaptation to high altitude.

Feasibility and effects on the gut microbiota of a 12-week high-intensity interval training plus lifestyle education intervention on inactive adults with celiac disease.

This study assessed the feasibility and benefits of high-intensity interval training (HIIT) plus lifestyle education among inactive adults with celiac disease. Forty-one participants were randomized to receive the intervention (HIIT plus lifestyle education; HIIT+) for 12 weeks or waitlist control (WLC). Testing was completed at baseline, immediately post-intervention, and 3 months post-intervention. Generalized estimating equations were used to assess changes in the outcome variables over time between the groups. Mean percent of age-predicted maximum heart rate was 97.9% and average rating of perceived exertion was 6.33 (out of 10) during HIIT intervals. Following the intervention, the HIIT+ showed enrichment in relative abundance of Parabacteroides and Defluviitaleaceae_UCG_011 while WLC showed enrichment in relative abundance of Roseburia intestinalis, Klebsiella, and Adlercreutzia. A unique set of taxa were differentially abundant between the groups at 3 months post-intervention. HIIT+ participants experienced a reduction in resting heart rate (-6.6 bpm) immediately post-intervention compared with WLC. Further research is needed to establish an optimal HIIT protocol that may improve maximal oxygen uptake and metabolic syndrome biomarkers. Findings from this pilot study provide preliminary evidence that an HIIT intervention is feasible for inactive adults with celiac disease and leads to favourable changes in resting heart rate alongside potentially beneficial shifts in gut microbiota. Trial registration number: ClinicalTrials.gov number NCT03520244. Novelty: HIIT leads to potentially beneficial changes in the gut microbiota of adults with celiac disease. An HIIT exercise intervention is feasible and well tolerated for patients with celiac disease.

The Gut Microbiota: A Potential Gateway to Improved Health Outcomes in Breast Cancer Treatment and Survivorship.

Breast cancer is the most frequently diagnosed cancer in women worldwide. The disease and its treatments exert profound effects on an individual's physical and mental health. There are many factors that impact an individual's risk of developing breast cancer, their response to treatments, and their risk of recurrence. The community of microorganisms inhabiting the gastrointestinal tract, the gut microbiota, affects human health through metabolic, neural, and endocrine signaling, and immune activity. It is through these mechanisms that the gut microbiota appears to influence breast cancer risk, response to treatment, and recurrence. A disrupted gut microbiota or state of 'dysbiosis' can contribute to a biological environment associated with higher risk for cancer development as well as contribute to negative treatment side-effects. Many cancer treatments have been shown to shift the gut microbiota toward dysbiosis; however, the microbiota can also be positively manipulated through diet, prebiotic and probiotic supplementation, and exercise. The objective of this review is to provide an overview of the current understanding of the relationship between the gut microbiota and breast cancer and to highlight potential strategies for modulation of the gut microbiota that could lead to improved clinical outcomes and overall health in this population.

Impact of age on host responses to diet-induced obesity: Development of joint damage and metabolic set points.

Background: Osteoarthritis is one of the leading causes of pain and disability worldwide, and a large percentage of patients with osteoarthritis are individuals who are also obese. In recent years, a series of animal models have demonstrated that obesity-inducing diets can result in synovial joint damage (both with and without the superimposition of trauma), which may be related to changes in percentage of body fat and a series of low-level systemic inflammatory mediators. Of note, there is a disparity between whether the dietary challenges commence at weaning, representing a weanling onset, or at skeletal maturity, representing an adult onset of obesity. We wished to evaluate the effect of the dietary exposure time and the age at which animals are exposed to a high-fat and high-sucrose (HFS) diet to determine whether these factors may result in disparate outcomes, as there is evidence suggesting that these factors result in differential metabolic disturbances. Based on dietary exposure time, we hypothesized that rats fed an HFS diet for 14 weeks from weaning (HFS Weanling) would demonstrate an increase in knee joint damage scores, whereas rats exposed to the HFS diet for 4 weeks, starting at 12 weeks of age (HFS Adult) and rats exposed to a standard chow diet (Chow) would not display an increase in knee joint damage scores. Methods: Male Sprague-Dawley rats were fed either an HFS diet for 14 weeks from weaning (HFS Weanling) or an HFS diet for 4 weeks, starting at 12 weeks of age (HFS Adult). At sacrifice, joints were scored using the modified Mankin Criteria, and serum was analyzed for a defined subset of inflammatory markers (Interleukin-6, leptin, monocyte chemoattractant protein-1, and tumor necrosis factor α). Results: When the HFS Weanling and HFS Adult groups were compared, both groups had a similar percent of body fat, although the HFS Weanling group had a significantly greater body mass than the HFS Adult group. The HFS Weanling and HFS Adult animals had a significant increase in body mass and percentage of body fat when compared to the Chow group. Although knee joint damage scores were low in all 3 groups, we found, contrary to our hypothesis, that the HFS Adult group had statistically significant greater knee joint damage scores than the Chow and HFS Weanling groups. Furthermore, we observed that the HFS Weanling group did not have significant differences in knee joint damage scores relative to the Chow group. Conclusion: These findings indicate that the HFS Weanling animals were better able to cope with the dietary challenge of an HFS diet than the HFS Adult group. Interestingly, when assessing various serum proinflammatory markers, no significant differences were detected between the HFS Adult and HFS Weanling groups. Although details regarding the mechanisms underlying an increase in knee joint damage scores in the HFS Adult group remain to be elucidated, these findings indicate that dietary exposure time maybe less important than the age at which an HFS diet is introduced. Moreover, increases in serum proinflammatory mediators do not appear to be directly linked to knee joint damage scores in the HFS Weanling group animals but may be partially responsible for the observed knee joint damage in the adults over the very short time of exposure to the HFS diet.

The chemo-gut study: investigating the long-term effects of chemotherapy on gut microbiota, metabolic, immune, psychological and cognitive parameters in young adult Cancer survivors; study protocol.

BACKGROUND: The gut microbiota is an important modulator of immune, metabolic, psychological and cognitive mechanisms. Chemotherapy adversely affects the gut microbiota, inducing acute dysbiosis, and alters physiological and psychological function. Cancer among young adults has risen 38% in recent decades. Understanding chemotherapy's long-term effects on gut microbiota and psycho-physiological function is critical to improve survivors' physical and mental health, but remains unexamined. Restoration of the gut microbiota via targeted therapies (e.g. probiotics) could potentially prevent or reverse the psycho-physiological deficits often found in young survivors following chemotherapy, ultimately leading to reduced symptom burden and improved health. METHODS: This longitudinal study investigates chemotherapy induced long-term gut dysbiosis, and associations between gut microbiota, and immune, metabolic, cognitive and psychological parameters using data collected at < 2 month (T1), 3-4 months (T2), and 5-6 months (T3) post-chemotherapy. Participants will be 18-39 year old blood or solid tumor cancer survivors (n = 50), and a healthy sibling, partner or friend as a control (n = 50). Gut microbiota composition will be measured from fecal samples using 16 s RNA sequencing. Psychological and cognitive patient reported outcome measures will include depression, anxiety, post-traumatic stress disorder symptoms, pain, fatigue, and social and cognitive function. Dual-energy X-ray Absorptiometry (DXA) will be used to measure fat and lean mass, and bone mineral concentration. Pro-inflammatory cytokines, C-reactive protein (CRP), lipopolysaccharide (LPS), serotonin, and brain derived neurotrophic factor (BDNF) will be measured in serum, and long-term cortisol will be assayed from hair. Regression and linear mixed model (LMM) analyses will examine associations across time points (T1 - T3), between groups, and covariates with gut microbiota, cognitive, psychological, and physiological parameters. CONCLUSION: Knowing what bacterial species are depleted after chemotherapy, how long these effects last, and the physiological mechanisms that may drive psychological and cognitive issues among survivors will allow for targeted, integrative interventions to be developed, helping to prevent or reverse some of the late-effects of treatment that many young cancer survivors face. This protocol has been approved by the Health Research Ethics Board of Alberta Cancer Committee (ID: HREBA.CC-19-0018).

Histological improvement of non-alcoholic steatohepatitis with a prebiotic: a pilot clinical trial.

PURPOSE: In obesity and diabetes the liver is highly susceptible to abnormal uptake and storage of fat. In certain individuals hepatic steatosis predisposes to the development of non-alcoholic steatohepatitis (NASH), a disease marked by hepatic inflammation and fibrosis. Although the precise pathophysiology of NASH is unknown, it is believed that the gut microbiota-liver axis influences the development of this disease. With few treatment strategies available for NASH, exploration of gut microbiota-targeted interventions is warranted. We investigated the therapeutic potential of a prebiotic supplement to improve histological parameters of NASH. METHODS: In a placebo-controlled, randomized pilot trial, 14 individuals with liver-biopsy-confirmed NASH [non-alcoholic fatty liver activity score (NAS) ≥ 5] were randomized to receive oligofructose (8 g/day for 12 weeks followed by 16 g/day for 24 weeks) or isocaloric placebo for 9 months. The primary outcome measure was the change in liver biopsy NAS score and the secondary outcomes included changes in body weight, body composition, glucose tolerance, inflammatory markers, and gut microbiota. RESULTS: Independent of weight loss, oligofructose improved liver steatosis relative to placebo and improved overall NAS score (P = 0.016). Bifidobacterium was enhanced by oligofructose, whereas bacteria within Clostridium cluster XI and I were reduced with oligofructose (P < 0.05). There were no adverse side effects that deterred individuals from consuming oligofructose for treatment of this disease. CONCLUSIONS: Independent of other lifestyle changes, prebiotic supplementation reduced histologically-confirmed steatosis in patients with NASH. Larger follow-up studies are warranted. CLINICAL TRIAL: This trial was registered at Clinicaltrials.com as NCT03184376.

Cross-Sectional Analysis of Overall Dietary Intake and Mediterranean Dietary Pattern in Patients with Crohn's Disease.

The primary objective of this study was to explore the macro- and micro-nutrient intakes and dietary patterns of patients with Crohn's disease (CD). Secondary objectives were to (a) compare the micronutrient intakes of CD patients with a representative sample of individuals, (b) describe the macro- and micronutrient intakes of male and female CD patients, and (c) describe Mediterranean diet scores (P-MDS) of male and female CD patients in remission that were recruited from an inflammatory bowel disease (IBD) clinic in Calgary, AB. Consecutive patients with ileal and/or colonic CD in endoscopic remission were recruited for participation in this cross-sectional study. Sixty-seven patients were enrolled with a mean age of 45, and a Body Mass Index (BMI) ≥ 25. Compared with the representative sample, patients with CD had similar energy, protein, carbohydrate, and total fat intake. However, polyunsaturated fats (PUFA), omega-6 and 3, and monounsaturated fats (MUFA) were lower in CD patients and dietary fiber intake was higher (p < 0.05). Vitamins C, D, thiamin, niacin, magnesium, phosphorus, zinc, and potassium were all significantly lower in all CD patients when compared to the representative sample (p < 0.05). Few patients with CD met the P-MDS criteria and overall scores were low (mean 4.5, Standard Deviation (SD) = 1.1 in males and 4.7, SD = 1.8 in females). The CD patients in this study had suboptimal dietary intakes and patterns and these data may be used to inform future dietary interventions in this population to improve intake.

Prevalence of comorbid conditions pre-existing and diagnosed at a tertiary care pediatric weight management clinic.

BACKGROUND: Childhood obesity places individuals at risk for a multitude of physical and mental health problems. The aim of this study was to assess the prevalence of obesity related comorbidities diagnosed prior to and after attending a tertiary care pediatric weight management clinic. METHODS: A cross sectional retrospective chart review of patients 2-17 years old seen in the weight management clinic at Alberta Children's Hospital from May 2012 to May 2014. RESULTS: A total of 199 patients were included in the review. Comorbidity prevalences were: hypertension 6 (3%), prediabetes 11 (5.5%), type 2 diabetes 3 (1.5%), dyslipidemia 105 (52.8%), non-alcoholic fatty liver disease 31 (15.6%), asthma 45 (22.6%), obstructive sleep apnea 21 (10.6%), and polycystic ovarian syndrome (PCOS) 9 (12% of females ≥10 years at the first visit). Concerns related to depression and anxiety were present in 20 (10.1%) and 25 (12.6%) patients respectively. The majority of comorbidities were identified prior to joining the clinic. Conditions requiring more specialized tests, such as diabetes and PCOS, were more commonly identified after joining the clinic. CONCLUSIONS: These results give further insight into the prevalence of obesity-related comorbidities in overweight and obese children and adolescents, and demonstrate the importance of screening for these known comorbidities. It is important to have the resources and an experienced multi-disciplinary team to follow children and their families through treatment.

Prebiotics Reduce Body Fat and Alter Intestinal Microbiota in Children Who Are Overweight or With Obesity.

BACKGROUND & AIMS: It might be possible to manipulate the intestinal microbiota with prebiotics or other agents to prevent or treat obesity. However, little is known about the ability of prebiotics to specifically modify gut microbiota in children with overweight/obesity or reduce body weight. We performed a randomized controlled trial to study the effects of prebiotics on body composition, markers of inflammation, bile acids in fecal samples, and composition of the intestinal microbiota in children with overweight or obesity. METHODS: We performed a single-center, double-blind, placebo-controlled trial of 2 separate cohorts (March 2014 and August 2014) at the University of Calgary in Canada. Participants included children, 7-12 years old, with overweight or obesity (>85th percentile of body mass index) but otherwise healthy. Participants were randomly assigned to groups given either oligofructose-enriched inulin (OI; 8 g/day; n=22) or maltodextrin placebo (isocaloric dose, controls; n=20) once daily for 16 weeks. Fat mass and lean mass were measured using dual-energy-x-ray absorptiometry. Height, weight, and waist circumference were measured at baseline and every 4 weeks thereafter. Blood samples were collected at baseline and 16 weeks, and analyzed for lipids, cytokines, lipopolysaccharide, and insulin. Fecal samples were collected at baseline and 16 weeks; bile acids were profiled using high-performance liquid chromatography and the composition of the microbiota was analyzed by 16S rRNA sequencing and quantitative polymerase chain reaction. The primary outcome was change in percent body fat from baseline to 16 weeks. RESULTS: After 16 weeks, children who consumed OI had significant decreases in body weight z-score (decrease of 3.1%), percent body fat (decrease of 2.4%), and percent trunk fat (decrease of 3.8%) compared with children given placebo (increase of 0.5%, increase of 0.05%, and decrease of 0.3%, respectively). Children who consumed OI also had a significant reduction in level of interleukin 6 from baseline (decrease of 15%) compared with the placebo group (increase of 25%). There was a significant decrease in serum triglycerides (decrease of 19%) in the OI group. Quantitative polymerase chain reaction showed a significant increase in Bifidobacterium spp. in the OI group compared with controls. 16S rRNA sequencing revealed significant increases in species of the genus Bifidobacterium and decreases in Bacteroides vulgatus within the group who consumed OI. In fecal samples, levels of primary bile acids increased in the placebo group but not in the OI group over the 16-week study period. CONCLUSIONS: In a placebo-controlled, randomized trial, we found a prebiotic (OI) to selectively alter the intestinal microbiota and significantly reduce body weight z-score, percent body fat, percent trunk fat, and serum level of interleukin 6 in children with overweight or obesity (Clinicaltrials.gov no: NCT02125955).

Oligofructose decreases serum lipopolysaccharide and plasminogen activator inhibitor-1 in adults with overweight/obesity.

OBJECTIVE: To determine the effect of prebiotic supplementation on metabolic endotoxemia and systemic inflammation in adults with overweight and obesity. METHODS: Samples from a previously conducted randomized, double-blind, placebo-controlled trial were used for analysis. Participants were randomized to 21 g of oligofructose (n = 20; BMI 30.4 kg/m2 ) or a maltodextrin placebo (n = 17; BMI 29.5 kg/m2 ) for 12 weeks. A total of 37 participants had samples available for the current analysis. Resistin, adiponectin, plasminogen activator inhibitor-1 (PAI-1), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), and macrophage chemoattractant protein-1 (MCP-1) were quantified using MILLIPLEX® assays. Lipopolysaccharide (LPS) was measured using PyroGene™ Recombinant Factor C Assay. RESULTS: Plasma LPS concentrations were reduced by 40% in the oligofructose group over 12 weeks compared to a 48% increase in the placebo group (P = 0.04). PAI-1, a risk factor for thrombosis, was reduced to a greater extent in the oligofructose group (-17.3 ± 2.6 ng/ml) compared to the placebo group (-9.7 ± 1.8 ng/ml; P = 0.03). Oligofructose did not affect IL-6, TNF-α, MCP-1, adiponectin, or resistin. CONCLUSIONS: Oligofructose reduces metabolic endotoxemia and PAI-1. Incorporating prebiotics into the diet through supplements or functional foods may help mitigate some markers of obesity-associated inflammation.

Dietary Intake and Associated Body Weight in Canadian Undergraduate Students Enrolled in Nutrition Education.

The primary purpose of this study was to describe dietary intakes among Canadian undergraduate students enrolled in an Introductory Nutrition course. A secondary objective was to determine food group servings associated with meeting more Dietary Reference Intakes (DRIs) of select nutrients and with a lower body mass index (BMI). Participants (n = 124, 20.7±3.2yrs) provided output from a 3-day dietary record and completed a physical activity/demographics questionnaire. Linear regression showed that the dietary intake associated with meeting the most DRIs included vegetables, fruits, protein foods, and dairy (p = 0.001). Protein foods were a positive predictor and fruit a negative predictor of BMI (p = 0.001 and p = 0.023 respectively). Males consumed more grains (p = 0.001), dairy (p = 0.04), protein foods (p < 0.001), empty calories (p = 0.007) and total calories than females (p < 0.001). A diet characterized by greater intake of vegetables, fruits, protein foods, and dairy was associated with a Canadian undergraduate population meeting the greatest number of nutrient requirements.

Patient-reported outcomes, body composition, and nutrition status in patients with head and neck cancer: Results from an exploratory randomized controlled exercise trial.

BACKGROUND: Patients with head and neck cancer experience loss of weight and muscle mass, decreased functioning, malnutrition, depression, and declines in quality of life during and after treatment. The purpose of this exploratory randomized study was to determine the optimal timing for the initiation of a lifestyle and progressive resistance exercise training intervention (during or after radiation therapy), as determined by intervention adherence and by comparing between-group outcomes across 24 weeks. METHODS: Sixty patients with head and neck cancer were randomized to engage in a 12-week lifestyle intervention and progressive resistance-training program either during radiation treatment or immediately after completion. The primary outcome of body composition--specifically, lean body mass, body mass index, and body fat--as well as secondary outcomes of fitness, quality of life, depression, and nutrition status were evaluated. RESULTS: The progressive resistance-training intervention carried out during treatment did not significantly influence the primary outcome of body composition, despite a significant increase in weekly physical activity reported by the intervention group. A small-to-medium intervention effect was noted for some secondary outcomes, including fitness, quality of life, and nutrition status. Regardless of whether patients received the immediate or delayed progressive resistance-training intervention, the analysis revealed a main effect of time on body composition, fitness, quality of life, depression, and nutritional scores. CONCLUSIONS: Although the intervention during treatment did not reduce the loss of lean body mass, delaying the exercise program until after treatment completion was associated with improved intervention adherence, a finding with important clinical implications.

Postnatal prebiotic fibre intake mitigates some detrimental metabolic outcomes of early overnutrition in rats.

PURPOSE: Overnutrition during early development has been linked to metabolic disease and obesity in adulthood. Interventions to ameliorate this metabolic malprogramming are needed. Our objective was to determine whether prebiotic fibre would reduce weight gain and improve satiety hormone profiles in rats overnourished during the suckling period. METHODS: Male Sprague-Dawley rats reared in small litter (SL 3 pups) or normal litter (NL 12 pups) were randomized at weaning to AIN-93 (control) or a 10 % oligofructose (OFS) diet for 16 weeks. Body composition, an oral glucose tolerance test for glucose and gut hormones, and gut microbiota were assessed. RESULTS: At weaning, body weight was higher in SL than in NL rats (P < 0.03). At 19 weeks, body weight was lower with OFS than control (P < 0.04). There was a diet × litter size interaction wherein OFS in SL rats reduced body fat (%) to levels seen in NL rats (P < 0.05). OFS attenuated the glucose response in SL but not in NL rats (P < 0.015). Independent of litter size, OFS decreased total AUC for glucose-dependent insulinotropic polypeptide (P < 0.002) and increased total AUC for peptide YY (P < 0.01) and glucagon-like peptide-1 (P < 0.04) when compared to control. OFS, not litter size, played the predominant role in altering gut microbiota which included increased bifidobacteria and Akkermansia muciniphila with OFS. CONCLUSIONS: Postnatal consumption of OFS by rats raised in SL was able to attenuate body fat and glycaemia to levels seen in NL rats. OFS appears to influence satiety hormone and gut microbiota response similarly in overnourished and control rats.

Evaluation of yellow pea fibre supplementation on weight loss and the gut microbiota: a randomized controlled trial.

BACKGROUND: Fibre intake among North Americans is currently less than half the recommended amount. Consumers are interested in food products that could promote weight loss and improve health. Consequently, evaluation of unique fibre sources with potential gut-mediated benefits for metabolic health warrants investigation. Our objective is to assess the effects of yellow pea fibre supplementation on weight loss and gut microbiota in an overweight and obese adult population. METHODS/DESIGN: In a double blind, placebo controlled, parallel group study, overweight and obese (BMI = 25-38) adults will be randomized to either a 15 g/d yellow pea fibre supplemented group or isocaloric placebo group for 12 weeks (n = 30/group). The primary outcome measure is a change in body fat from baseline to 12 weeks. Secondary outcomes include glucose tolerance, appetite regulation, serum lipids and inflammatory markers. Anthropometric data (height, weight, BMI, and waist circumference) and food intake (by 3-day weighed food records) will be measured at baseline and every 4 weeks thereafter. Subjective ratings of appetite will be recorded by participants at home on a weekly basis using validated visual analogue scales. At week 0 and at the end of the study (week 12), an ad libitum lunch buffet protocol for objective food intake measures and dual-energy X-ray absorptiometry (DXA) scan for body composition will be completed. Participants will be instructed not to change their exercise habits during the 12 week study. Glucose and insulin will be measured during an oral glucose tolerance test at weeks 0 and 12. Levels of lipids and CRP will be measured and inflammatory markers (adiponectin, leptin, TNF-α, IL-6 and IL-8) in the serum will be quantified using Milliplex kits. Mechanisms related to changes in gut microbiota, serum and fecal water metabolomics will be assessed. DISCUSSION: Globally the development of functional foods and functional food ingredients are critically needed to curb the rise in metabolic disease. This project will assess the potential of yellow pea fibre to improve weight control via gut-mediated changes in metabolic health in overweight and obese adults. TRIAL REGISTRATION: ClinicalTrials.gov (NCT01719900) Registered October 23, 2012.