The metabolic and inflammatory processes that are implicated in the development of cardiovascular diseases are under control of the biological clock. While skeletal muscle function exhibits... Show moreThe metabolic and inflammatory processes that are implicated in the development of cardiovascular diseases are under control of the biological clock. While skeletal muscle function exhibits circadian rhythms, it is unclear to what extent the beneficial health effects of exercise are restricted to unique time windows. We aimed to study whether the timing of exercise training differentially modulates the development of atherosclerosis and elucidate underlying mechanisms. We endurance-trained atherosclerosis-prone female APOE*3-Leiden.CETP mice fed a Western-type diet, a well-established human-like model for cardiometabolic diseases, for 1 h five times a week for 4 weeks either in their early or in their late active phase on a treadmill. We monitored metabolic parameters, the development of atherosclerotic lesions in the aortic root and assessed the composition of the gut microbiota. Late, but not early, exercise training reduced fat mass by 19% and the size of early-stage atherosclerotic lesions by as much as 29% compared to sedentary animals. No correlation between cholesterol exposure and lesion size was evident, as no differences in plasma lipid levels were observed, but circulating levels of the pro-inflammatory markers ICAM-1 and VCAM-1 were reduced with late exercise. Strikingly, we observed a time-of-day-dependent effect of exercise training on the composition of the gut microbiota as only late training increased the abundance of gut bacteria producing short-chain fatty acids with proposed anti-inflammatory properties. Together, these findings indicate that timing is a critical factor to the beneficial anti-atherosclerotic effects of exercise with a great potential to further optimize training recommendations for patients. Show less
Schonke, M.; Ying, Z.X.; Kovynev, A.; Panhuis, W.I.H.; Binnendijk, A.; Poel, S. van der; ... ; Rensen, P.C.N. 2023
The metabolic and inflammatory processes that are implicated in the development of cardiovascular diseases are under control of the biological clock. While skeletal muscle function exhibits... Show moreThe metabolic and inflammatory processes that are implicated in the development of cardiovascular diseases are under control of the biological clock. While skeletal muscle function exhibits circadian rhythms, it is unclear to what extent the beneficial health effects of exercise are restricted to unique time windows. We aimed to study whether the timing of exercise training differentially modulates the development of atherosclerosis and elucidate underlying mechanisms. We endurance-trained atherosclerosis-prone female APOE*3-Leiden.CETP mice fed a Western-type diet, a well-established human-like model for cardiometabolic diseases, for 1h five times a week for 4weeks either in their early or in their late active phase on a treadmill. We monitored metabolic parameters, the development of atherosclerotic lesions in the aortic root and assessed the composition of the gut microbiota. Late, but not early, exercise training reduced fat mass by 19% and the size of early-stage atherosclerotic lesions by as much as 29% compared to sedentary animals. No correlation between cholesterol exposure and lesion size was evident, as no differences in plasma lipid levels were observed, but circulating levels of the pro-inflammatory markers ICAM-1 and VCAM-1 were reduced with late exercise. Strikingly, we observed a time-of-day-dependent effect of exercise training on the composition of the gut microbiota as only late training increased the abundance of gut bacteria producing short-chain fatty acids with proposed anti-inflammatory properties. Together, these findings indicate that timing is a critical factor to the beneficial anti-atherosclerotic effects of exercise with a great potential to further optimize training recommendations for patients. Show less
Schönke, M.; Ying, Z.X.; Kovynev, A.; Panhuis, W.I.H.; Binnendijk, A.; Poel, S. van der; ... ; Rensen, P.C.N. 2023
The metabolic and inflammatory processes that are implicated in the development of cardiovascular diseases are under control of the biological clock. While skeletal muscle function exhibits... Show moreThe metabolic and inflammatory processes that are implicated in the development of cardiovascular diseases are under control of the biological clock. While skeletal muscle function exhibits circadian rhythms, it is unclear to what extent the beneficial health effects of exercise are restricted to unique time windows. We aimed to study whether the timing of exercise training differentially modulates the development of atherosclerosis and elucidate underlying mechanisms. We endurance-trained atherosclerosis-prone female APOE*3-Leiden.CETP mice fed a Western-type diet, a well-established human-like model for cardiometabolic diseases, for 1 h five times a week for 4 weeks either in their early or in their late active phase on a treadmill. We monitored metabolic parameters, the development of atherosclerotic lesions in the aortic root and assessed the composition of the gut microbiota. Late, but not early, exercise training reduced fat mass by 19% and the size of early-stage atherosclerotic lesions by as much as 29% compared to sedentary animals. No correlation between cholesterol exposure and lesion size was evident, as no differences in plasma lipid levels were observed, but circulating levels of the pro-inflammatory markers ICAM-1 and VCAM-1 were reduced with late exercise. Strikingly, we observed a time-of-day-dependent effect of exercise training on the composition of the gut microbiota as only late training increased the abundance of gut bacteria producing short-chain fatty acids with proposed anti-inflammatory properties. Together, these findings indicate that timing is a critical factor to the beneficial anti-atherosclerotic effects of exercise with a great potential to further optimize training recommendations for patients. Show less
Pre-clinical studies suggest that circulating oxylipins, i.e., the oxidation products of polyunsaturated fatty acids (PUFAs), modulate gut microbiota composition in mice, but there is no... Show morePre-clinical studies suggest that circulating oxylipins, i.e., the oxidation products of polyunsaturated fatty acids (PUFAs), modulate gut microbiota composition in mice, but there is no information available in humans. Therefore, this study aimed to investigate the relationship between omega-3 and omega-6 derived oxylipins plasma levels and fecal microbiota composition in a cohort of young adults. 80 young adults (74% women; 21.9 +/- 2.2 years old) were included in this cross-sectional study. Plasma levels of oxylipins were measured using liquid chromatography-tandem mass spectrometry. Fecal microbiota composition was analyzed by V3-V4 16S rRNA gene sequencing. We observed that plasma levels of omega-3 derived oxylipins were positively associated with the relative abundance of Clostridium cluster IV genus (Firmicutes phylum; rho >= 0.415, p <= 0.009) and negatively associated with the relative abundance of Sutterella genus (Proteobacteria phylum; rho >= -0.270, p <= 0.041), respectively. Moreover, plasma levels of omega-6 derived oxylipins were negatively associated with the relative abundance of Acidaminococcus and Phascolarctobacterium genera (Firmicutes phylum; all rho >= -0.263, p <= 0.024), as well as Sutterella, Succinivibrio, and Gemmiger genera (Proteobacteria phylum; all rho >= -0.263, p <= 0.024). Lastly, the ratio between omega-6 and omega-3 oxylipins plasma levels was negatively associated with the relative abundance of Clostridium cluster IV genus (Firmicutes phylum; rho = -0.334, p = 0.004) and Butyricimonas genus (Bacteroidetes phylum; rho = -0.292, p = 0.014). In conclusion, our results show that the plasma levels of omega-3 and omega-6 derived oxylipins are associated with the relative abundance of specific fecal bacteria genera. Show less
BACKGROUND: The relationship between gut microbiota and in vivo coronary plaque characteristics has not been reported. This study was conducted to investigate the relationship between gut... Show moreBACKGROUND: The relationship between gut microbiota and in vivo coronary plaque characteristics has not been reported. This study was conducted to investigate the relationship between gut microbiota and coronary plaque characteristics in patients with coronary artery disease.METHODS AND RESULTS: Patients who underwent both optical coherence tomography and intravascular ultrasound imaging and provided stool and blood specimens were included. The composition of gut microbiota was evaluated using 16S rRNA sequencing. A total of 55 patients were included. At the genus level, 2 bacteria were associated with the presence of thin-cap fibroatheroma, and 9 bacteria were associated with smaller fibrous cap thickness. Among them, some bacteria had significant associations with inflammatory/prothrombotic biomarkers. Dysgonomonas had a positive correlation with interleukin-6, Paraprevotella had a positive correlation with fibrinogen and negative correlation with high-density lipoprotein cholesterol, Succinatimonas had positive correlations with fibrinogen and homocysteine, and Bacillus had positive correlations with fibrinogen and high-sensitivity C-reactive protein. In addition, Paraprevotella, Succinatimonas, and Bacillus were also associated with greater plaque volume. Ten bacteria were associated with larger fibrous cap thickness. Some were associated with protective biomarker changes; Anaerostipes had negative correlations with trimethylamine N-oxide, tumor necrosis factor alpha, and interleukin-6, and Dielma had negative correlations with trimethylamine N-oxide, white blood cells, plasminogen activator inhibitor-1, and homocysteine, and a positive correlation with high-density lipoprotein cholesterol.CONCLUSIONS: Bacteria that were associated with vulnerable coronary plaque phenotype and greater plaque burden were identified. These bacteria were also associated with elevated inflammatory or prothrombotic biomarkers. Show less
Background This study characterized gut microbiota and its diet-related activity in children with intestinal failure (IF) receiving parenteral nutrition (PN) compared with those of healthy controls... Show moreBackground This study characterized gut microbiota and its diet-related activity in children with intestinal failure (IF) receiving parenteral nutrition (PN) compared with those of healthy controls (HC) and in relation to disease characteristics. Methods The fecal microbiota and short-chain fatty acids (SCFAs) were measured in 15 IF patients (n = 68) and 25 HC (n = 25). Results Patients with IF had a lower bacterial load (P = .003), diversity (P < .001), evenness (P < .001) and richness (P = 0.006) than HC. Patients with surgical IF had lower diversity (P < .039) than those with functional IF. Propionic acid and butyric acid (p < .001) were lower and d-lactate and l-lactate were higher (p < 0.001) in IF patients than in HC. The energy supplied by PN (%PN) was negatively associated with microbiota diversity and SCFA profile. IF patients had more Escherichia-Shigella (P = .006), Cronobacter (P = .001), and Staphylococcus (Operational Taxonomic Unit 14, P < .001) and less Faecalibacterium (P < 0.001) and Ruminococcus 1 and 2 (P < .001). Duration of PN (P = .005), %PN (P = .005), and fiber intake (P = .011) were predictive of microbiota structure. Higher intake of enteral nutrition was associated with microbiota structure and function closer to those of HC. Conclusions Microbiota composition and its diet-related function are altered in IF, with depletion of beneficial SCFAs and species and supraphysiological increase of potentially harmful pathobionts. The influence of this compositional and functional microbial dysbiosis on patients' outcomes and management warrants further exploration. Show less
Diet and body mass index (BMI) have been shown to affect the gut microbiota of children, but studies are largely performed in developed countries. Here, we conducted a cross-sectional investigation... Show moreDiet and body mass index (BMI) have been shown to affect the gut microbiota of children, but studies are largely performed in developed countries. Here, we conducted a cross-sectional investigation on the differences in the bacterial gut microbiota between normal-weight and overweight urban Filipino children, and determined the relationship between their energy, macronutrient and dietary fiber intakes, and their gut microbiota composition and diversity. Forty-three children (normal-weight,n= 32; overweight,n= 11) participated in the study. Energy and fiber intakes were collected using a semi-quantitative Food Frequency Questionnaire (FFQ). The gut microbiota was profiled using 16S rRNA gene amplicon sequencing of the V3-V4 region. The diet of the children was a mixture of traditional and Western patterns. There were no significant differences in energy, macronutrients and energy-adjusted fiber intakes between the normal-weight and overweight groups, but there were significantly more children meeting the recommended fiber intake in the overweight group. Alpha and beta bacterial diversities did not significantly differ between weight groups. Relative abundance ofBifidobacterium,TuricibacterandClostridiaceae 1were higher in the normal-weight than overweight children, andLachnospirawas higher in overweight children. Show less
Amaruddin, A.I.; Hamid, F.; Koopman, J.P.R.; Muhammad, M.; Brienen, E.A.T.; Lieshout, L. van; ... ; Zwittink, R.D. 2020
To understand the relationship between the gut microbiota and the health profile of Indonesians, it is important to elucidate the characteristics of the bacterial communities that prevail in this... Show moreTo understand the relationship between the gut microbiota and the health profile of Indonesians, it is important to elucidate the characteristics of the bacterial communities that prevail in this population. To this end, we profiled the faecal bacterial community of 140 Indonesian schoolchildren in urban Makassar. The core microbiota of Indonesian schoolchildren consisted ofBifidobacterium,Collinsella, and multiple members of theLachnospiraceaeandRuminicoccaceaefamilies, but the relative abundance of these taxa varied greatly among children. Socioeconomic status (SES) was the main driver for differences in microbiota composition. Multiple bacterial genera were differentially abundant between high and low SES children, includingBifidobacterium, Lactobacillus, Prevotella, andEscherichia-Shigella. In addition, the microbiota of high SES children was less diverse and strongly associated with body mass index (BMI). In low SES children, helminth infection was prevalent and positively associated withOlsenella, Enterohabdus,Lactobacillus, andMogibacteriumabundance, while negatively associated with relative abundance ofPrevotella. Protozoa infection was also prevalent, and positively associated withRikenellaceae,while it was negatively associated with the relative abundance ofRomboutsiaandPrevotella. In conclusion, Indonesian schoolchildren living in urban Makassar share a core microbiota, but their microbiota varies in diversity and relative abundance of specific bacterial taxa depending on socioeconomic status, nutritional status, and intestinal parasites infection. Show less
Gut microbiota composition in patients with Clostridioides difficile colonization is not well investigated. We aimed to identify bacterial signatures associated with resistance and susceptibility... Show moreGut microbiota composition in patients with Clostridioides difficile colonization is not well investigated. We aimed to identify bacterial signatures associated with resistance and susceptibility to C. difficile colonization (CDC) and infection (CDI). Therefore, gut microbiota composition from patients with CDC (n = 41), with CDI (n = 41), and without CDC (controls, n = 43) was determined through 16S rRNA gene amplicon sequencing. Bacterial diversity was decreased in CDC and CDI patients (p < 0.01). Overall microbiota composition was significantly different between control, CDC, and CDI patients (p = 0.001). Relative abundance of Clostridioides (most likely C. difficile) increased stepwise from controls to CDC and CDI patients. In addition, differential abundance analysis revealed that CDI patients' gut microbiota was characterized by significantly higher relative abundance of Bacteroides and Veillonella than CDC patients and controls. Control patients had significantly higher Eubacterium hallii and Fusicatenibacter abundance than colonized patients. Network analysis indicated that Fusicatenibacter was negatively associated with Clostridioides in CDI patients, while Veillonella was positively associated with Clostridioides in CDC patients. Bacterial microbiota diversity decreased in both CDC and CDI patients, but harbored a distinct microbiota. Eubacterium hallii and Fusicatenibacter may indicate resistance against C. difficile colonization and subsequent infection, while Veillonella may indicate susceptibility to colonization and infection by C. difficile. Show less
The gut microbiome is critical in providing resistance against colonization by exogenous microorganisms. The mechanisms via which the gut microbiota provide colonization resistance (CR) have not... Show moreThe gut microbiome is critical in providing resistance against colonization by exogenous microorganisms. The mechanisms via which the gut microbiota provide colonization resistance (CR) have not been fully elucidated, but they include secretion of antimicrobial products, nutrient competition, support of gut barrier integrity, and bacteriophage deployment. However, bacterial enteric infections are an important cause of disease globally, indicating that microbiota-mediated CR can be disturbed and become ineffective. Changes in microbiota composition, and potential subsequent disruption of CR, can be caused by various drugs, such as antibiotics, proton pump inhibitors, antidiabetics, and antipsychotics, thereby providing opportunities for exogenous pathogens to colonize the gut and ultimately cause infection. In addition, the most prevalent bacterial enteropathogens, including Clostridioides diflicile, Salmonella enterica serovar Typhimurium, enterohemorrhagic Escherichia coli, Shigella flexneri, Campylobacter jejuni, Vibrio cholerae, Yersinia enterocolitica, and Listeria monocytogenes, can employ a wide array of mechanisms to overcome colonization resistance. This review aims to summarize current knowledge on how the gut microbiota can mediate colonization resistance against bacterial enteric infection and on how bacterial enteropathogens can overcome this resistance. Show less
The nutritional requirements of preterm infants are unique and challenging to meet in neonatal care, yet crucial for their growth, development and health. Normally, the gut microbiota has distinct... Show moreThe nutritional requirements of preterm infants are unique and challenging to meet in neonatal care, yet crucial for their growth, development and health. Normally, the gut microbiota has distinct metabolic capacities, making their role in metabolism of dietary components indispensable. In preterm infants, variation in microbiota composition is introduced while facing a unique set of environmental conditions. However, the effect of such variation on the microbiota's metabolic capacity and on the preterm infant's growth and development remains unresolved. In this review, we will provide a holistic overview on the development of the preterm gut microbiota and the unique environmental conditions contributing to this, in addition to maturation of the gastrointestinal tract and immune system in preterm infants. The role of prematurity, as well as the role of human milk, in the developmental processes is emphasized. Current research stresses the early life gut microbiota as cornerstone for simultaneous development of the gastrointestinal tract and immune system. Besides that, literature provides clues that prematurity affects growth and development. As such, this review is concluded with our hypothesis that prematurity of the gut microbiota may be an inconspicuous clinical challenge in achieving optimal feeding besides traditional challenges, such as preterm breast milk composition, high nutritional requirements and immaturity of the gastrointestinal tract and immune system. A better understanding of the metabolic capacity of the gut microbiota and its impact on gut and immune maturation in preterm infants could complement current feeding regimens in future neonatal care and thereby facilitate growth, development and health in preterm infants. Show less
Obieglo, K.; Wijck, Y. van; Kleijn, S. de; Smits, H.H.; Taube, C. 2014
