Gut diversity and the resistome as biomarkers of febrile neutropenia outcome in paediatric oncology patients undergoing hematopoietic stem cell transplantation.

The gut microbiota of paediatric oncology patients undergoing a conditioning regimen before hematopoietic stem cell transplantation is recently considered to play role in febrile neutropenia. Disruption of commensal microbiota and evolution of opportune pathogens community carrying a plethora of antibiotic-resistance genes play crucial role. However, the impact, predictive role and association of patient´s gut resistome in the course of the therapy is still to be elucidated. We analysed gut microbiota composition and resistome of 18 paediatric oncology patients undergoing hematopoietic stem cell transplantation, including 12 patients developing febrile neutropenia, hospitalized at The Bone Marrow Transplantation Unit of the National Institute of Children´s disease in Slovak Republic and healthy individuals (n = 14). Gut microbiome of stool samples obtained in 3 time points, before hematopoietic stem cell transplantation (n = 16), one week after hematopoietic stem cell transplantation (n = 16) and four weeks after hematopoietic stem cell transplantation (n = 14) was investigated using shotgun metagenome sequencing and bioinformatical analysis. We identified significant decrease in alpha-diversity and nine antibiotic-resistance genes msr(C), dfrG, erm(T), VanHAX, erm(B), aac(6)-aph(2), aph(3)-III, ant(6)-Ia and aac(6)-Ii, one week after hematopoietic stem cell transplantation associated with febrile neutropenia. Multidrug-resistant opportune pathogens of ESKAPE, Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae and Escherichia coli found in the gut carried the significant subset of patient's resistome. Over 50% of patients treated with trimethoprim/sulfamethoxazole, piperacillin/tazobactam and amikacin carried antibiotic-resistance genes to applied treatment. The alpha diversity and the resistome of gut microbiota one week after hematopoietic stem cell transplantation is relevant predictor of febrile neutropenia outcome after hematopoietic stem cell transplantation. Furthermore, the interindividual diversity of multi-drug resistant opportunistic pathogens with variable portfolios of antibiotic-resistance genes indicates necessity of preventive, personalized approach.

High Diversity but Monodominance of Multidrug-Resistant Bacteria in Immunocompromised Pediatric Patients with Acute Lymphoblastic Leukemia Developing GVHD Are Not Associated with Changes in Gut Mycobiome.

Graft-versus-host disease (GvHD) is a severe complication after hematopoietic stem cell transplantation (HSCT). Our study focused on identifying multidrug-resistant (MDR) gut bacteria associated with GvHD-prone guts and association with gut microbiota (GM) diversity, bacteriome, and mycobiome composition in post-HSCT patients. We examined 11 pediatric patients with acute lymphoblastic leukemia (ALL), including six with GvHD, within three time points: seven days pre-HSCT, seven days post-, and 28 days post-HSCT. The gut microbiome and its resistome were investigated using metagenomic sequencing, taxonomically classified with Kraken2, and statistically evaluated for significance using appropriate tests. We observed an increase in the abundance of MDR bacteria, mainly Enterococcus faecium strains carrying msr(C), erm(T), aac(6')-li, dfrG, and ant(6)-la genes, in GvHD patients one week post-HSCT. Conversely, non-GvHD patients had more MDR beneficial bacteria pre-HSCT, promoting immunosurveillance, with resistance genes increasing one-month post-HSCT. MDR beneficial bacteria included the anti-inflammatory Bacteroides fragilis, Ruminococcus gnavus, and Turicibacter, while most MDR bacteria represented the dominant species of GM. Changes in the gut mycobiome were not associated with MDR bacterial monodominance or GvHD. Significant α-diversity decline (Shannon index) one week and one month post-HSCT in GvHD patients (p < 0.05) was accompanied by increased Pseudomonadota and decreased Bacteroidota post-HSCT. Our findings suggest that MDR commensal gut bacteria may preserve diversity and enhance immunosurveillance, potentially preventing GvHD in pediatric ALL patients undergoing HSCT. This observation has therapeutic implications.

The effect of physical exercise and dairy probiotics (Lactobacillus casei) on gut microbiome in childhood cancer survivors.

Gut microbial dysbiosis persists months after intensive cancer treatment in children and adolescents. This prospective study compared the intestinal microbiome of children 1-3 years after completion of Berlin-Frankfurt-Münster protocol (BFM)-based pediatric ALL (PALL) treatment and healthy controls. To induce a favorable shift in the bacterial composition of the intestines in PALL with gut microbiome disruptions, 8 weeks of physical activity and probiotic consumption were used. Blood analyses and 16S rRNA sequencing for the gut microbiome were performed on 16 pediatric cases and 16 healthy controls. Significant differences in bacterial diversity were found between pre- and post-intervention, respectively (Shannon index, 3.22±0.45 vs. 3.47±0.24, p=0.04; Simpson index, 0.10±0.05 vs. 0.06±0.02, p=0.02; and Chao1 index, 693.88±238.58 vs. 794.23±116.34, p=0.04). Furthermore, the increase in the relative abundance of Lactobacillus casei (5.04E-03±1.62E-02 vs. 2.92E-02±5.03E-02, p=0.04) and the increase in some strains of Veillonella, a bacterial genus recently linked to improved physical fitness, were identified. Promisingly, the exercise program combined with dairy probiotics increased bacterial richness and diversity.

Gut Microbiota and Serum Metabolites in Individuals with Class III Obesity Without Type 2 Diabetes Mellitus: Pilot Analysis.

Background: Gut microbial composition seems to change in association with prediabetes. The purpose of this prospective cross-sectional study was to compare the composition of gut microbiota and energy metabolites between individuals with class III obesity but without type 2 diabetes mellitus (OB) and healthy normal weight controls. Methods: The subjects of this prospective cross-sectional study were participants recruited from a previous clinical trial (No: NCT02325804), with intervention focused on weight loss. We recruited 19 OB [mean age ± standard deviation (SD) was 35.4 ± 7.0 years, mean body mass index (BMI) ± SD was 48.8 ± 6.7 kg/m2] and 23 controls (mean age ± SD was 31.7 ± 14.8 years, mean BMI ± SD was 22.2 ± 1.7 kg/m2). Their fecal microbiota was categorized using specific primers targeting the V1-V3 region of 16S rDNA, whereas serum metabolites were characterized by nuclear magnetic resonance spectroscopy. Multivariate statistical analysis and Random Forest models were applied to discriminate predictors with the highest variable importance. Results: We observed a significantly lower microbial α-diversity (P = 0.001) and relative abundance of beneficial bacterium Akkermansia (P = 0.001) and the short-chain fatty acid-producing bacteria Eubacterium hallii (P = 0.019), Butyrivibrio (P = 0.024), Marvinbryantia (P = 0.010), and Coprococcus (P = 0.050) and a higher abundance of the pathogenic bacteria Bilophila (P = 0.018) and Fusobacterium (P = 0.022) in OB compared with controls. Notably, the Random Forest machine learning analysis identified energy metabolites (citrate and acetate), HOMA-IR, and insulin as important predictors capable of discriminating between OB and controls. Conclusions: Our results suggest that changes in gut microbiota and in serum acetate and citrate are additional promising biomarkers before progression to Type 2 diabetes. The non-invasive manipulation of gut microbiota composition in OB through a healthy lifestyle, thus, offers a new approach for managing class III obesity and associated disorders. ClinicalTrials.gov identifier: NCT02325804.

Effect of High-intensity Training and Probiotics on Gut Microbiota Diversity in Competitive Swimmers: Randomized Controlled Trial.

BACKGROUND: Physical exercise has favorable effects on the structure of gut microbiota and metabolite production in sedentary subjects. However, little is known whether adjustments in an athletic program impact overall changes of gut microbiome in high-level athletes. We therefore characterized fecal microbiota and serum metabolites in response to a 7-week, high-intensity training program and consumption of probiotic Bryndza cheese. METHODS: Fecal and blood samples and training logs were collected from young competitive male (n = 17) and female (n = 7) swimmers. Fecal microbiota were categorized using specific primers targeting the V1-V3 region of 16S rDNA, and serum metabolites were characterized by NMR-spectroscopic analysis and by multivariate statistical analysis, Spearman rank correlations, and Random Forest models. RESULTS: We found higher α-diversity, represented by the Shannon index value (HITB-pre 5.9 [± 0.4]; HITB-post 6.4 [± 0.4], p = 0.007), (HIT-pre 5.5 [± 0.6]; HIT-post 5.9 [± 0.6], p = 0.015), after the end of the training program in both groups independently of Bryndza cheese consumption. However, Lactococcus spp. increased in both groups, with a higher effect in the Bryndza cheese consumers (HITB-pre 0.0021 [± 0.0055]; HITB-post 0.0268 [± 0.0542], p = 0.008), (HIT-pre 0.0014 [± 0.0036]; HIT-post 0.0068 [± 0.0095], p = 0.046). Concomitant with the increase of high-intensity exercise and the resulting increase of anaerobic metabolism proportion, pyruvate (p[HITB] = 0.003; p[HIT] = 0.000) and lactate (p[HITB] = 0.000; p[HIT] = 0.030) increased, whereas acetate (p[HITB] = 0.000; p[HIT] = 0.002) and butyrate (p[HITB] = 0.091; p[HIT] = 0.019) significantly decreased. CONCLUSIONS: Together, these data demonstrate a significant effect of high-intensity training (HIT) on both gut microbiota composition and serum energy metabolites. Thus, the combination of intensive athletic training with the use of natural probiotics is beneficial because of the increase in the relative abundance of lactic acid bacteria.

Gut Microbiome Suffers from Hematopoietic Stem Cell Transplantation in Childhood and Its Characteristics Are Positively Associated with Intra-Hospital Physical Exercise.

Gut microbiome impairment is a serious side effect of cancer treatment. The aim of this study was to identify the effects of hematopoietic stem cell transplantation (HSCT) treatment on gut microbiota composition in children with acute lymphoblastic leukemia (ALL). Fecal microbiotas were categorized using specific primers targeting the V1-V3 region of 16S rDNA in eligible pediatric ALL patients after HSCT (n = 16) and in healthy controls (Ctrl, n = 13). An intra-hospital exercise program was also organized for child patients during HSCT treatment. Significant differences in gut microbiota composition were observed between ALL HSCT and Ctrl with further negative effects. Plasma C-reactive protein correlated positively with the pathogenic bacteria Enterococcus spp. and negatively with beneficial bacteria Butyriccocus spp. or Akkermansia spp., respectively (rs = 0.511, p = 0.05; rs = -0.541, p = 0.04; rs = -0.738, p = 0.02). Bacterial alpha diversity correlated with the exercise training characteristics. Therefore, specific changes in the microbiota of children were associated with systemic inflammation or the ability to exercise physically during HSCT treatment.

Association Between Mechanical, Physiological, and Technical Parameters With Canoe Slalom Performance: A Systematic Review.

This study aimed to systematically review studies that evaluated and compared mechanical, physiological, and technical parameters with the performance of slalom athletes. PubMed, SPORTDiscuss, and Scopus databases were searched until September 10, 2021, with no restriction of published data. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses guided the study's screening and quality assessment performed by an external reviewer using a 16-checklist item. A search of the databases identified 125 studies, but only eight were eligible, including a total sample of 117 male athletes. Four reports only associated mechanical or technical parameters with the performance of the paddler. Concerning the remaining studies, only one correlated physiological data, and the others associated more than one parameter with race time. Most of the eligible reports presented significant associations between mechanical/physiological components and slalom performance. Eligible studies support that high-force development during a slalom race is a relevant parameter for performance. Aerobic metabolism is highly required during slalom tasks and is inversely associated with race time, although it may not increase the chances of winning medals. Few reports have associated canoe slalom performance with technical components, and further research should focus on this matter.

Bioaccessibility and Bioavailability of Minerals in Relation to a Healthy Gut Microbiome.

Adequate amounts of a wide range of micronutrients are needed by body tissues to maintain health. Dietary intake must be sufficient to meet these micronutrient requirements. Mineral deficiency does not seem to be the result of a physically active life or of athletic training but is more likely to arise from disturbances in the quality and quantity of ingested food. The lack of some minerals in the body appears to be symbolic of the modern era reflecting either the excessive intake of empty calories or a negative energy balance from drastic weight-loss diets. Several animal studies provide convincing evidence for an association between dietary micronutrient availability and microbial composition in the gut. However, the influence of human gut microbiota on the bioaccessibility and bioavailability of trace elements in human food has rarely been studied. Bacteria play a role by effecting mineral bioavailability and bioaccessibility, which are further increased through the fermentation of cereals and the soaking and germination of crops. Moreover, probiotics have a positive effect on iron, calcium, selenium, and zinc in relation to gut microbiome composition and metabolism. The current literature reveals the beneficial effects of bacteria on mineral bioaccessibility and bioavailability in supporting both the human gut microbiome and overall health. This review focuses on interactions between the gut microbiota and several minerals in sport nutrition, as related to a physically active lifestyle.

Strenuous Physical Training, Physical Fitness, Body Composition and Bacteroides to Prevotella Ratio in the Gut of Elderly Athletes.

Regular physical activity seems to have a positive effect on the microbiota composition of the elderly, but little is known about the added possible benefits of strenuous endurance training. To gain insight into the physiology of the elderly and to identify biomarkers associated with endurance training, we combined different omics approaches. We aimed to investigate the gut microbiome, plasma composition, body composition, cardiorespiratory fitness, and muscle strength of lifetime elderly endurance athletes (LA) age 63.5 (95% CI 61.4, 65.7), height 177.2 (95% CI 174.4, 180.1) cm, weight 77.8 (95% CI 75.1, 80.5) kg, VO2max 42.4 (95% CI 39.8, 45.0) ml.kg-1.min-1 (n = 13) and healthy controls age 64.9 (95% CI 62.1, 67.7), height 174.9 (95% CI 171.2, 178.6) cm, weight 83.4 (95% CI 77.1, 89.7) kg, VO2max 28.9 (95% CI 23.9, 33.9), ml.kg-1.min-1 (n = 9). Microbiome analysis was performed on collected stool samples further subjected to 16S rRNA gene analysis. NMR-spectroscopic analysis was applied to determine and compare selected blood plasma metabolites mostly linked to energy metabolism. The machine learning (ML) analysis discriminated subjects from the LA and CTRL groups using the joint predictors Bacteroides 1.8E + 00 (95% CI 1.1, 2.5)%, 3.8E + 00 (95% CI 2.7, 4.8)% (p = 0.002); Prevotella 1.3 (95% CI 0.28, 2.4)%, 0.1 (95% CI 0.07, 0.3)% (p = 0.02); Intestinimonas 1.3E-02 (95% CI 9.3E-03, 1.7E-02)%, 5.9E-03 (95% CI 3.9E-03, 7.9E-03)% (p = 0.002), Subdoligranulum 7.9E-02 (95% CI 2.5E-02, 1.3E-02)%, 3.2E-02 (95% CI 1.8E-02, 4.6E-02)% (p = 0.02); and the ratio of Bacteroides to Prevotella 133 (95% CI -86.2, 352), 732 (95% CI 385, 1079.3) (p = 0.03), leading to an ROC curve with AUC of 0.94. Further, random forest ML analysis identified VO2max, BMI, and the Bacteroides to Prevotella ratio as appropriate, joint predictors for discriminating between subjects from the LA and CTRL groups. Although lifelong endurance training does not bring any significant benefit regarding overall gut microbiota diversity, strenuous athletic training is associated with higher cardiorespiratory fitness, lower body fat, and some favorable gut microbiota composition, all factors associated with slowing the rate of biological aging.

A Possible Preventive Role of Physically Active Lifestyle during the SARS-CoV-2 Pandemic; Might Regular Cold-Water Swimming and Exercise Reduce the Symptom Severity of COVID-19?

The objective of this study was to investigate the incidence and course of COVID-19 and the risk of an upper respiratory tract infection in a group of people with physically active lifestyles. Data were collected anonymously using an online survey platform during December 2020. The age of participants ranged from 18 to 65 years. Out of 2343 participants, 11.5% overcame COVID-19 infection. Relative to the control group (CTRL), physically active, cold-water swimmers (PACW) did not exhibit a lower risk of incidence for COVID-19 (RR 1.074, CI 95% (0.710-1.625). However, PACW had a higher chance of having an asymptomatic course of COVID-19 (RR 2.321, CI 95% (0.836-6.442); p < 0.05) and a higher chance of only having an acute respiratory infection once or less per year than CTRL (RR 1.923, CI 95% (1.1641-2.253); p < 0.01). Furthermore, PACW exhibited a lower incidence of acute respiratory infection occurring more than twice per year (RR 0.258, CI 95% (0.138-0.483); p < 0.01). Cold-water swimming and physical activity may not lessen the risk of COVID-19 in recreational athletes. However, a physically active lifestyle might have a positive effect on the rate of incidence of acute respiratory infection and on the severity of COVID-19 symptoms.

The Efficacy of Short-Term Weight Loss Programs and Consumption of Natural Probiotic Bryndza Cheese on Gut Microbiota Composition in Women.

Weight loss interventions with probiotics have favourable effects on gut microbiota composition and derived metabolites. However, little is known about whether the consumption of natural probiotics, such as Bryndza cheeses, brings similar benefits. The purpose of the study was to find the effect of short-term weight loss programs and Bryndza cheese consumption on the structure of the gut microbiota, microbiota-derived metabolites and body composition in middle-aged women. We conducted a randomised controlled intervention study. Twenty-two female participants with a body fat percentage ≥25% underwent a short weight loss program (4 weeks). Subjects were randomised to either the control or intervention group according to diet. The intervention group comprised 13 participants, whose diet contained 30 g of "Bryndza" cheese daily (WLPB). The control group comprised nine participants without the regular consumption of Bryndza cheese (WLP) in their diet. Both interventions lead to a significant and favourable change of BMI, body fat, waist circumference and muscle mass. Moreover, the relative abundance of Erysipelotrichales significantly increased in both groups. However, the relative abundance of lactic acid bacteria (Lactobacillales, Streptococcaceae, Lactococcus and Streptococcus) significantly increased only in the WLPB group. Furthermore, short-chain fatty acid producers Phascolarctobacterium and Butyricimonas increased significantly in the WLPB group. A short-term weight loss program combined with Bryndza cheese consumption improves body composition and increases the abundance of lactic acid bacteria and short-chain fatty acid producers in middle-aged women.

Gut Microbiota Diversity in Lean Athletes Is Associated with Positive Energy Balance.

INTRODUCTION: In contrast to obesity, little is known about the human lean phenotype associated with gut microbiota composition. OBJECTIVE: We aimed to investigate whether the bacterial composition of lean athletes with a positive energy balance differs from the equal-calorie food group. METHODS: Twenty-four male participants were included in this cross-sectional study: lean athletes with a positive energy balance (LA, n 12) and control group athletes (CTRLs, n 12). Nutritional data, resting and total energy expenditure, and body composition were determined. DNA was extracted from stool samples and subjected to 16S rRNA gene analysis. RESULTS: We found 7 differentially abundant bacterial taxa between the LA and CTRL groups. Of those, 5 were significantly less abundant and 2 were enriched in the LA group. The following categories significantly associated with the community structure were identified: body fat parameters, BMI, energy intake and expenditure, oxygen consumption, and respiratory exchange ratio. CONCLUSIONS: Although we are far from a detailed interpretation of lean human body maintenance, the primary findings of our study suggest that gut microbial composition may be a factor influencing the regulation of weight gain in lean athletes with a positive energy balance.

Comparison of Aerobic and Muscular Power Between Junior/U23 Slalom and Sprint Paddlers: An Analysis of International Medalists and Non-medalists.

This study aimed to compare the aerobic power (treadmill running) and muscle power (bench press and bench pull) of Junior/U23 paddlers from Slovakia who won medals in international championships with that of those who did not take the podium. Forty-three Slovak Junior/U23 paddlers (sprint = 24, medalists = 8, non-medalists = 16; slalom = 19, medalists = 11, non-medalists = 8) were tested in 2018 and 2019 after the world championships. The maximal oxygen uptake (VO2max) and the velocity at maximal oxygen uptake (vVO2max) were determined by the incremental running protocol (0% slope and 1 km⋅h-1 increments every minute until volitional exhaustion). Mean maximal power from the entire concentric phase was recorded during bench press and bench pull exercises by the validated TENDO weightlifting analyzer. No interaction was obtained between medal and canoe discipline for VO2max (p = 0.069, F = 3.495), vVO2max (p = 0.552, F = 0.361) and absolute (bench press: p = 0.486, F = 0.495; bench pull: p = 0.429, F = 0.640) or relative (bench press: p = 0.767, F = 0.089; bench pull: p = 0.696, F = 0.155) mean maximal power. Conversely, a significant effect for the medal on the bench press (absolute p = 0.017, F = 6.170; relative p = 0.043, F = 4.384) and the bench pull (absolute p = 0.041, F = 4.470) mean maximal power were observed. Our study indicates the absolute mean power on the bench press as a prerequisite for success in international Junior/U23 championships of slalom and sprint canoeing. However, the mean power on bench pull seems to have a deeper influence on sprint paddlers when compared to slalom athletes. Regarding the aerobic power, the data from the treadmill testing did not reveal outcomes between medalists and non-medalists. This result can be associated with the lack of specificity of the incremental treadmill testing for canoeing, and future studies are encouraged to propose specific protocols to compare the aerobic power of medalists and non-medalists in international slalom and sprint championships.

Road to the Olympics: physical fitness of medalists of the Canoe Sprint Junior European and World Championship events over the past 20 years.

BACKGROUND: In this article we aimed to find out whether there is a difference in physiological, anthropometric and power variables between medalists in junior international Championship events (MJCH) and the remaining members of the national team (NT) in flat water canoe sprint. METHODS: Sixty male junior kayakers from Slovak NT were tested annually between years 1995 and 2016. Sixteen of them won at least one medal (gold, silver or bronze) at junior international Championship. Exercise capacity assessment on treadmill running (TR) and kayak ergometer (KE), anthropometric and muscle power measurements were performed between years 1995 and 2016. RESULTS: MJCH were on average by 10% better in TR speed and KE power output at VO2max than the rest of NT (19.72±0.8 vs. 18±1.0 km.h-1, P<0.01, ES=1.84; 206.6±21.5 vs. 182.3±25.5 W, P<0.01, ES=0.99, respectively). Similarly mean maximal power in bench press and bench pull was higher in MJCH (522.9±72.0 vs. 464.3±69.0 W, P<0.01; ES=0.84; 629.15±63.3 vs. 571.6±58.7 W, P<0.01; ES=0.96, respectively). CONCLUSIONS: These data show that an athlete has to be on average by 10% better in physical fitness than the rest of NT to take podium position at canoe sprint junior international Championship. Prosperous juniors are further successful at senior Championship events and Olympics. We assume that high level of physical fitness in junior age is not a guarantee but a prerequisite for a successful future career.