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Cardiovascular diseases (CVDs) encompass various conditions affecting the heart and its blood vessels and are often linked with oral microbes. Our data analysis aimed to identify oral bacteria from other non-oral sites (i.e., gut, arterial plaque and cultured blood) that could be linked with CVDs. Taxonomic profiling identified bacteria to the species level and compared with the Human Oral Microbiome Database (HOMD). The oral bacteria in the gut, cultured blood and arterial plaque samples were catalogued, with their average frequency calculated for each sample. Additionally, data were filtered by comparison with the Human Microbiome Project (HMP) database. We identified 17,243 microbial species, of which 410 were present in the HOMD database and further denominated as "oral", and were found in at least one gut sample, but only 221 and 169 species were identified in the cultured blood and plaque samples, respectively. Of the 410 species, 153 were present solely in oral-associated environments after comparison with the HMP database, irrespective of their presence in other body sites. Our results suggest a potential connection between the presence of specific species of oral bacterial and occurrence of CVDs. Detecting these oral bacterial species in non-oral sites of patients with CVDs could help uncover the link between oral health and general health, including cardiovascular conditions via bacterial translocation.
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Enfermedades Cardiovasculares , Microbiota , Placa Aterosclerótica , Humanos , Microbiota/genética , Bacterias/genética , MetagenomaRESUMEN
ARTICLE TITLE AND BIBLIOGRAPHIC INFORMATION: Castro Dos Santos NC, Furukawa MV, Oliveira-Cardoso I, Cortelli JR, Feres M, Van Dyke T, Rovai ES. Does the use of omega-3 fatty acids as an adjunct to nonsurgical periodontal therapy provide additional benefits in the treatment of periodontitis? A systematic review and meta-analysis. J Periodontal Res. 2022 Jun;57(3):435-447. doi: 10.1111/jre.12984. Epub 2022 Mar 3. PMID: 35243637. SOURCE OF FUNDING: This study was funded by São Paulo Research Foundation (FAPESP) under awards 2020/05875-9 (to NCCS), 2020/05874-2 (to MF), and 2019/14846-5 (to ESR). TYPE OF STUDY/DESIGN: Systematic review and meta-analysis.
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Ácidos Grasos Omega-3 , Periodontitis , Humanos , Brasil , Suplementos Dietéticos , Ácidos Grasos Omega-3/uso terapéutico , Periodontitis/terapia , Revisiones Sistemáticas como Asunto , Metaanálisis como AsuntoRESUMEN
BACKGROUND: Periodontitis is a chronic multifactorial inflammatory disease, that leads to tooth loss and is associated with other systemic diseases. The role of dietary fibre in the prevention and management of periodontal diseases is not well understood. The objective of this systematic review and meta-analysis was to assess how an intake of dietary fibre affects periodontal diseases in humans and any concomitant effects on systemic inflammation. METHODOLOGY: Human interventional studies investigating the effects of oral fibre intake on various clinical parameters of periodontal diseases were included. Search strategy with MeSH and free-text search terms was performed on the following database: CINAHL Complete, EMBASE, MEDLINE, SciVerse Scopus®, and Web of Science Core Collection on 21 October 2021 and updated on 19 February 2023 to identify relevant studies. Articles were filtered using the Covidence© web-based platform software. Data were pooled using random effects meta-analysis. RESULTS: From all databases, a total of 19,971 studies were obtained. Upon title and abstract screening, 101 studies were included for full-text screening. Upon full-text screening, six studies were included for analysis. Of these, five were randomised controlled trials, and one was a sequential feeding trial involving fibre-rich daily diet for a 4-8 weeks period. Fibre-rich dietary intervention significantly reduced Clinical Attachment Loss/Level by 0.48 mm/tooth (95% CI, -0.63 to -0.33, p < 0.001), Bleeding On Probing by 27.57% sites/tooth (95% CI -50.40 to -4.74, p = 0.02), Periodontal Inflamed Surface Area by 173.88 mm2 (95% CI -288.06 to -59.69, p = 0.003), Plaque Index by 0.02 (95% CI -0.04 to -0.00, p = 0.04), and Gingival Index by 0.41 (95% -0.67 to -0.16, p= 0.002). A non-significant reduction was observed for Probing Depth (-0.17 mm/tooth; 95% CI, -0.37 to 0.02, p = 0.09). CONCLUSIONS: Fibre-rich dietary interventions are associated with a reduction of clinical and particularly inflammatory markers of periodontal diseases. This shows a promising effect of dietary fibre as an intervention for inflammatory conditions like periodontal diseases.
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Background: Periodontitis is a chronic inflammatory condition affecting the supporting structures of a tooth in the oral cavity. The relationship between dietary fiber and periodontitis is poorly understood. The objective of this systematic review is to investigate if an intake of dietary fiber modulates periodontal disease in animal models and any concomitant effects on systemic inflammation, microbiota and their metabolites. Methods: Animal studies using periodontitis models with any form of fiber intervention were included. Studies with comorbidities that were mutually inclusive with periodontitis and animals with physiological conditions were excluded. Search strategy with MeSH and free-text search terms were finalized and performed on the 22nd of September 2021.CINAHL Complete, EMBASE, MEDLINE, SciVerse Scopus® and Web of Science Core Collection databases were used to identify studies. SYRCLE's risk of bias tool and CAMARADES were used for quality assessment. Results were synthesized utilizing Covidence© web-based platform software to remove duplicates, and the remaining studies were manually filtered. Results: A total of 7,141 articles were retrieved from all databases. Out of 24 full-text articles assessed for eligibility, four studies (n = 4) were included. Four studies involved the use of ß-(1,3/1,6)-glucan (n = 3) and mannan oligosaccharide (n = 1) at differing dosages for different study durations. All studies utilized a ligature-induced model of periodontitis in rats, either Wistar (n = 3) or Sprague-Dawley (n = 1). A dose-dependent relationship between the increased fiber intake and decrease in alveolar bone loss and pro-inflammatory markers was observed. Conclusion: The number of included studies is limited and narrow in scope. They highlight the importance of pre-clinical trials in this field with broader dietary fiber intervention groups before proceeding to clinical trials. The use of dietary fiber as an intervention shows promise in the reduction of inflammatory conditions like periodontitis. However, further research is required to delineate the relationship between diet and its effects on microbiota and their metabolites such as short chain fatty acids in animal models of periodontitis.
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Oral health is vital to general health and well-being for all ages, and as with other chronic conditions, oral health problems increase with age. There is a bi-directional link between nutrition and oral health, in that nutrition affects the health of oral tissues and saliva, and the health of the mouth may affect the foods consumed. Evidence suggests that a healthy diet generally has a positive impact on oral health in older adults. Although studies examining the direct link between oral health and protein intake in older adults are limited, some have explored the relationship via malnutrition, which is also prevalent among older adults. Protein-energy malnutrition (PEM) may be associated with poor oral health, dental caries, enamel hypoplasia, and salivary gland atrophy. This narrative review presents the theoretical evidence on the impact of dietary protein and amino acid composition on oral health, and their combined impact on overall health in older adults.
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Caries Dental , Desnutrición Proteico-Calórica , Humanos , Anciano , Salud Bucal , Caries Dental/prevención & control , Estado Nutricional , Proteínas en la DietaRESUMEN
Advanced glycation end-products (AGEs) are heterogeneous compounds formed when excess sugars condense with the amino groups of nucleic acids and proteins. Increased AGEs are associated with insulin resistance and poor glycemic control. Recently, inflamed periodontal tissues and certain oral bacteria were observed to increase the local and systemic AGE levels in both normoglycemic and hyperglycemic individuals. Although hyperglycemia induced AGE and its effect on the periodontal tissues is known, periodontitis as an endogenous source of AGE formation is not well explored. Hence, this systematic review is aimed to explore, for the first time, whether inflamed periodontal tissues and periodontal pathogens have the capacity to modulate AGE levels in individuals with or without T2DM and how this affects the glycemic load. Six electronic databases were searched using the following keywords: (Periodontitis OR Periodontal disease OR Periodontal Inflammation) AND (Diabetes mellitus OR Hyperglycemia OR Insulin resistance) AND Advanced glycation end products. The results yielded 1140 articles, of which 13 articles were included for the review. The results showed that the mean AGE levels in gingival crevicular fluid was higher in individuals with diabetes mellitus and periodontitis (521.9 pg/mL) compared to healthy individuals with periodontitis (234.84 pg/mL). The serum AGE levels in normoglycemic subjects having periodontitis was higher compared to those without periodontitis (15.91 ng/mL vs. 6.60 ng/mL). Tannerella forsythia, a common gram-negative anaerobe periodontal pathogen in the oral biofilm, was observed to produce methylglyoxal (precursor of AGE) in the gingival tissues. Increased AGE deposition and activate of AGE receptors was noted in the presence of periodontitis in both normoglycemic and hyperglycemic individuals. Hence, it can be concluded that periodontitis can modulate the local and systemic levels of AGE levels even in absence of hyperglycemia. This explains the bidirectional relationship between periodontitis and development of prediabetes, incident diabetes, poor glycemic control, and insulin resistance.
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Diabetes Mellitus , Hiperglucemia , Resistencia a la Insulina , Periodontitis , Humanos , Hiperglucemia/complicaciones , Periodontitis/complicaciones , Periodoncio/metabolismoRESUMEN
AIM: The aim was to assess two macronutrient interventions in a 2 × 2 factorial dietary design to determine their effects on oral health. MATERIALS AND METHODS: Participants (65-75 years old) with a body mass index between 20 and 35 kg/m2 of a larger randomized control trial who consented to an oral health assessment were recruited. They had ad libitum access to one of four experimental diets (omnivorous higher fat or higher carbohydrate, semi-vegetarian higher fat or higher carbohydrate) for 4 weeks. The periodontal examination included periodontal probing depth (PPD), clinical attachment level (CAL), and bleeding on probing. Oral plaque and gingival crevicular fluid (GCF) were collected before and after the intervention. RESULTS: Between baseline and follow up, the number of sites with a CAL <5 mm (mean difference [MD] -5.11 ± 9.68, p = .039) increased and the GCF amount (MD -23.42 ± 39.42 Periotron Units [PU], p = .050) decreased for the semi-vegetarian high-fat diet. For the mean proportion of sites with PPD reduction of >1 mm and CAL gain of >1 mm, significant differences were calculated between the diets investigated. The clinical parameters were not associated with changes in the oral microbiota. CONCLUSIONS: The results of this study provided evidence that a semi-vegetarian high-fat diet provides benefits to clinical parameters of periodontal health. This study is registered in ClinicalTrials.gov (ACTRN12616001606471).
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Líquido del Surco Gingival , Anciano , Carbohidratos , Proteínas en la Dieta , Humanos , Pérdida de la Inserción Periodontal , Índice PeriodontalRESUMEN
CONTEXT: Consumption of dietary macronutrients is associated with the progression of a wide range of inflammatory diseases, either by direct modulation of host immune response or via microbiome. This includes periodontitis, a disease affecting tooth-supporting tissues. OBJECTIVE: The aim of this work was to systematically review studies focusing on the effect of macronutrient (ie, carbohydrate, protein, fat) intake on periodontitis in rodents. DATA SOURCES: Electronic searches were performed in February 2021 using the PubMed and Web of Science databases. Out of 883 articles reviewed, 23 studies were selected for additional analysis. DATA EXTRACTION: Investigators extracted relevant data, including author names; the year of publication; article title; macronutrient composition; number and species of animals and their age at the start of the experiment; intervention period; method of periodontitis induction; and primary and secondary periodontitis outcomes. Quality assessment was done using the risk-of-bias tool for animal studies. After completing the data extraction, descriptive statistical information was obtained. DATA ANALYSIS: High intakes of dietary cholesterol, saturated fatty acids, and processed carbohydrates such as sucrose, and protein-deficient diets were positively associated with periodontitis in rodents. This included greater amounts of alveolar bone loss, more lesions on periodontal tissues, and dental plaque accumulation. In contrast, high doses of milk basic protein in diets and diets with a high ratio of ω-3 to ω-6 fatty acids were negatively associated with periodontitis in rodents. CONCLUSION: This work highlights the fact that, despite the large body of evidence linking macronutrients with inflammation and ageing, overall there is little information on how dietary nutrients affect periodontitis in animal models. In addition, there is inconsistency in data due to differences in methodology, outcome measurement, and dietary formulation. More studies are needed to examine the effects of different dietary macronutrients on periodontitis and investigate the underlying biological mechanisms.
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Periodontitis , Roedores , Animales , Dieta , Carbohidratos de la Dieta , Ácidos Grasos , Humanos , Nutrientes , Periodontitis/epidemiologíaRESUMEN
BACKGROUND: Donor selection is an important factor influencing the engraftment and efficacy of fecal microbiota transplantation (FMT) for complex conditions associated with microbial dysbiosis. However, the degree, variation, and stability of strain engraftment have not yet been assessed in the context of multiple donors. METHODS: We conducted a double-blinded randomized control trial of FMT in 87 adolescents with obesity. Participants were randomized to receive multi-donor FMT (capsules containing the fecal microbiota of four sex-matched lean donors) or placebo (saline capsules). Following a bowel cleanse, participants ingested a total of 28 capsules over two consecutive days. Capsules from individual donors and participant stool samples collected at baseline, 6, 12, and 26 weeks post-treatment were analyzed by shotgun metagenomic sequencing allowing us to track bacterial strain engraftment and its functional implications on recipients' gut microbiomes. RESULTS: Multi-donor FMT sustainably altered the structure and the function of the gut microbiome. In what was effectively a microbiome competition experiment, we discovered that two donor microbiomes (one female, one male) dominated strain engraftment and were characterized by high microbial diversity and a high Prevotella to Bacteroides (P/B) ratio. Engrafted strains led to enterotype-level shifts in community composition and provided genes that altered the metabolic potential of the community. Despite our attempts to standardize FMT dose and origin, FMT recipients varied widely in their engraftment of donor strains. CONCLUSION: Our study provides evidence for the existence of FMT super-donors whose microbiomes are highly effective at engrafting in the recipient gut. Dominant engrafting male and female donor microbiomes harbored diverse microbial species and genes and were characterized by a high P/B ratio. Yet, the high variability of strain engraftment among FMT recipients suggests the host environment also plays a critical role in mediating FMT receptivity. TRIAL REGISTRATION: The Gut Bugs trial was registered with the Australian New Zealand Clinical Trials Registry ( ACTRN12615001351505 ). TRIAL PROTOCOL: The trial protocol is available at https://bmjopen.bmj.com/content/9/4/e026174 . Video Abstract.
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Disbiosis , Trasplante de Microbiota Fecal , Adolescente , Australia , Disbiosis/terapia , Heces , Femenino , Humanos , Masculino , Obesidad/terapia , Resultado del TratamientoRESUMEN
BACKGROUND: The first report of children born very preterm (<32 weeks of gestation) having insulin resistance was made 16 years ago. However, neonatal care has improved since. Thus, we aimed to assess whether children born very preterm still have lower insulin sensitivity than term controls. METHODS: Participants were prepubertal children aged 5 to 11 years born very preterm (<32 weeks of gestation; n = 51; 61% boys) or at term (37-41 weeks; n = 50; 62% boys). Frequently sampled intravenous glucose tolerance tests were performed, and insulin sensitivity was calculated using Bergman's minimal model. Additional clinical assessments included anthropometry, body composition using whole-body dual-energy X-ray absorptiometry scans, clinic blood pressure, and 24-hour ambulatory blood pressure monitoring. RESULTS: Children born very preterm were 0.69 standard deviation score (SDS) lighter (P < .001), 0.53 SDS shorter (P = .003), and had body mass index 0.57 SDS lower (P = .003) than children born at term. Notably, children born very preterm had insulin sensitivity that was 25% lower than term controls (9.4 vs 12.6 × 10-4 minutes-1 ·[mU/L]; P = .001). Other parameters of glucose metabolism, including fasting insulin levels, were similar in the two groups. The awake systolic blood pressure (from 24-hour monitoring) tended to be 3.1 mm Hg higher on average in children born very preterm (P = .054), while the clinic systolic blood pressure was 5.4 mm Hg higher (P = .002). CONCLUSIONS: Lower insulin sensitivity remains a feature of children born very preterm, despite improvements in neonatal intensive care. As reported in our original study, our findings suggest the defect in insulin action in prepubertal children born very pretermis primarily peripheral and not hepatic.
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Resistencia a la Insulina , Factores de Edad , Presión Sanguínea , Índice de Masa Corporal , Estudios de Casos y Controles , Niño , Preescolar , Femenino , Edad Gestacional , Prueba de Tolerancia a la Glucosa , Humanos , Recien Nacido Extremadamente Prematuro , Recién Nacido , Masculino , Factores de RiesgoRESUMEN
Importance: Treatment of pediatric obesity is challenging. Preclinical studies in mice indicated that weight and metabolism can be altered by gut microbiome manipulation. Objective: To assess efficacy of fecal microbiome transfer (FMT) to treat adolescent obesity and improve metabolism. Design, Setting, and Participants: This randomized, double-masked, placebo-controlled trial (October 2017-March 2019) with a 26-week follow-up was conducted among adolescents aged 14 to 18 years with a body mass index (BMI; calculated as weight in kilograms divided by height in meters squared) of 30 or more in Auckland, New Zealand. A total of 87 individuals took part-565 individuals responded to advertisements, 328 were ineligible, and 150 declined participation. Clinical data were analyzed from September 2019 to May 2020. Interventions: Single course of oral encapsulated fecal microbiome from 4 healthy lean donors of the same sex or saline placebo. Main Outcomes and Measures: Primary outcome was BMI standard deviation score at 6 weeks using intention-to-treat analysis. Secondary outcomes included body composition, cardiometabolic parameters, well-being, and gut microbiome composition. Results: Eighty-seven participants (59% female adolescents, mean [SD] age 17.2 [1.4] years) were randomized 1:1, in groups stratified by sex, to FMT (42 participants) or placebo (45 participants). There was no effect of FMT on BMI standard deviation score at 6 weeks (adjusted mean difference [aMD] -0.026; 95% CI -0.074, 0.022). Reductions in android-to-gynoid-fat ratio in the FMT vs placebo group were observed at 6, 12, and 26 weeks, with aMDs of -0.021 (95% CI, -0.041 to -0.001), -0.023 (95% CI, -0.043 to -0.003), and -0.029 (95% CI, -0.049 to -0.008), respectively. There were no observed effects on insulin sensitivity, liver function, lipid profile, inflammatory markers, blood pressure, total body fat percentage, gut health, and health-related quality of life. Gut microbiome profiling revealed a shift in community composition among the FMT group, maintained up to 12 weeks. In post-hoc exploratory analyses among participants with metabolic syndrome at baseline, FMT led to greater resolution of this condition (18 to 4) compared with placebo (13 to 10) by 26 weeks (adjusted odds ratio, 0.06; 95% CI, 0.01-0.45; P = .007). There were no serious adverse events recorded throughout the trial. Conclusions and Relevance: In this randomized clinical trial of adolescents with obesite, there was no effect of FMT on weight loss in adolescents with obesity, although a reduction in abdominal adiposity was observed. Post-hoc analyses indicated a resolution of undiagnosed metabolic syndrome with FMT among those with this condition. Further trials are needed to confirm these results and identify organisms and mechanisms responsible for mediating the observed benefits. Trial Registration: Australian New Zealand Clinical Trials Registry Identifier: ACTRN12615001351505.
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Trasplante de Microbiota Fecal , Microbioma Gastrointestinal/fisiología , Obesidad Infantil , Calidad de Vida , Adolescente , Índice de Masa Corporal , Método Doble Ciego , Trasplante de Microbiota Fecal/efectos adversos , Trasplante de Microbiota Fecal/métodos , Femenino , Humanos , Masculino , Monitoreo Fisiológico/métodos , Nueva Zelanda , Obesidad Infantil/metabolismo , Obesidad Infantil/fisiopatología , Obesidad Infantil/psicología , Obesidad Infantil/terapia , Resultado del TratamientoRESUMEN
Metabolic diseases are increasing among adolescents with obesity. Although the reported prevalence of metabolic syndrome is approximately 30% worldwide, its prevalence is largely unknown among New Zealand adolescents. Therefore, we assessed the health of adolescents with obesity (BMI ≥ 30 kg/m2) enrolled in a randomised clinical trial (Gut Bugs Trial), to identify the prevalence of undiagnosed comorbidities. Assessments included anthropometry, 24-h ambulatory blood pressure monitoring, and insulin sensitivity. We report on baseline data (pre-randomisation) on 87 participants (14-18 years; 59% females), with mean BMI 36.9 ± 5.3 kg/m2 (BMI SDS 3.33 ± 0.79). Approximately 40% of participants had undiagnosed metabolic syndrome, which was twice as common among males. Half (53%) had pre-diabetes and 92% a reduction in insulin sensitivity. Moreover, 31% had pre-hypertension/hypertension, 69% dyslipidaemia, and 25% abnormal liver function. Participants with class III obesity had a greater risk of metabolic syndrome than those with classes I/II [relative risk 1.99 (95% CI 1.19, 3.34)]. Risks for pre-hypertension/hypertension and inflammation were also greater among those with class III obesity. We identified a high prevalence of undiagnosed comorbidities among adolescents with obesity in New Zealand. As adolescent obesity tracks into adulthood, early interventions are needed to prevent progression to overt cardiometabolic diseases.
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Síndrome Metabólico/epidemiología , Obesidad Infantil/epidemiología , Estado Prediabético/epidemiología , Enfermedades no Diagnosticadas/epidemiología , Adolescente , Monitoreo Ambulatorio de la Presión Arterial , Índice de Masa Corporal , Comorbilidad , Dislipidemias/epidemiología , Femenino , Humanos , Resistencia a la Insulina , Masculino , Nueva Zelanda/epidemiología , Prehipertensión/epidemiología , Prevalencia , Factores Socioeconómicos , Circunferencia de la CinturaRESUMEN
The melanocortin peptides have an important role in regulating body weight and appetite. Mice that lack the desacetyl-α-MSH and α-MSH peptides (Pomctm1/tm1) develop obesity. This effect is exacerbated by a high fat diet (HFD). However, development of obesity in female Pomctm1/tm1 mice during chronic HFD conditions is not fully accounted for by the increased energy intake. We hypothesized that the protection against chronic HFD-induced obesity imparted by MSH peptides in females is mediated by sex-specific alterations in the gut structure and gut microbiota. We determined that female WT mice had reduced jejunum villus length and increased crypt depth in response to chronic HFD. WT males and Pomctm1/tm1 mice lacked this adaptation to a chronic HFD. Both Pomctm1/tm1 genotype and chronic HFD were significantly associated with gut microbiota composition. Sex-specific associations between Pomctm1/tm1 genotype and gut microbiota were observed in the presence of a chronic HFD. Pomctm1/tm1 females had significantly reduced fecal acetate and propionate concentrations when compared to WT females. We conclude that MSH peptides influence jejunum villus length, crypt depth and the structure of the gut microbiota. These effects favor reduced nutrient absorption and occur in addition to the recognized roles of desacetyl-α-MSH and α-MSH peptides in appetite control.
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Dieta Alta en Grasa/efectos adversos , Microbioma Gastrointestinal/efectos de los fármacos , Hormonas Estimuladoras de los Melanocitos/metabolismo , Ácido Acético/metabolismo , Animales , Femenino , Genotipo , Masculino , Ratones , Ratones Endogámicos C57BL , Análisis Multivariante , Obesidad/metabolismo , Proopiomelanocortina/metabolismo , Propionatos/metabolismo , ARN Ribosómico 16S/metabolismo , alfa-MSH/metabolismoRESUMEN
Preterm infants are exposed to major perinatal, post-natal, and early infancy events that could impact on the gut microbiome. These events include infection, steroid and antibiotic exposure, parenteral nutrition, necrotizing enterocolitis, and stress. Studies have shown that there are differences in the gut microbiome during the early months of life in preterm infants. We hypothesized that differences in the gut microbial composition and metabolites in children born very preterm persist into mid-childhood. Participants were healthy prepubertal children aged 5-11 years who were born very preterm (≤32 weeks of gestation; n = 51) or at term (37-41 weeks; n = 50). We recorded the gestational age, birth weight, mode of feeding, mode of birth, age, sex, and the current height and weight of our cohort. We performed a multi'omics [i.e., 16S rRNA amplicon and shotgun metagenomic sequencing, SPME-GCMS (solid-phase microextraction followed by gas chromatography-mass spectrometry)] analysis to investigate the structure and function of the fecal microbiome (as a proxy of the gut microbiota) in our cross-sectional cohort. Children born very preterm were younger (7.8 vs. 8.3 years; p = 0.034), shorter [height-standard deviation score (SDS) 0.31 vs. 0.92; p = 0.0006) and leaner [BMI (body mass index) SDS -0.20 vs. 0.29; p < 0.0001] than the term group. Children born very preterm had higher fecal calprotectin levels, decreased fecal phage richness, lower plasma arginine, lower fecal branched-chain amino acids and higher fecal volatile (i.e., 3-methyl-butanoic acid, butyrolactone, butanoic acid and pentanoic acid) profiles. The bacterial microbiomes did not differ between preterm and term groups. We speculate that the observed very preterm-specific changes were established in early infancy and may impact on the capacity of the very preterm children to respond to environmental changes.
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Bacteriófagos , Microbioma Gastrointestinal , Niño , Estudios Transversales , Femenino , Humanos , Lactante , Recién Nacido , Recien Nacido Prematuro , Embarazo , ARN Ribosómico 16S/genéticaRESUMEN
INTRODUCTION: Animal studies showed that germ-free mice inoculated with normal mouse gut bacteria developed obesity, insulin resistance and higher triglyceride levels, despite similar food intake. In humans, an association has been found between obesity and gut microbiome dysbiosis. However, gut microbiome transfer has not been evaluated for the treatment of human obesity. We will examine the effectiveness of gut microbiome transfer using encapsulated material for the treatment of obesity in adolescents. METHODS AND ANALYSIS: A two-arm, double-blind, placebo-controlled, randomised clinical trial of a single course of gut microbiome transfer will be conducted in 80 obese [body mass index (BMI) ≥30 kg/m2] adolescents (males and females, aged 14-18 years) in Auckland, New Zealand. Healthy lean donors (males and females, aged 18-28 years) will provide fresh stool samples from which bacteria will be isolated and double encapsulated. Participants (recipients) will be randomised at 1:1 to control (placebo) or treatment (gut microbiome transfer), stratified by sex. Recipients will receive 28 capsules over two consecutive mornings (~14 mL of frozen microbial suspension or saline). Clinical assessments will be performed at baseline, 6, 12 and 26 weeks, and will include: anthropometry, blood pressure, fasting metabolic markers, dietary intake, physical activity levels and health-related quality of life. Insulin sensitivity (Matsuda index), gut microbiota population structure characterised by 16S rRNA amplicon sequencing and body composition (using dual-energy X-ray absorptiometry) will be assessed at baseline, 6, 12 and 26 weeks. 24-hour ambulatory blood pressure monitoring will be performed at baseline and at 6 weeks. The primary outcome is BMI SD scores (SDS) at 6 weeks, with BMI SDS at 12 and 26 weeks as secondary outcomes. Other secondary outcomes include insulin sensitivity, adiposity (total body fat percentage) and gut microbial composition at 6, 12 and 26 weeks. Statistical analysis will be performed on the principle of intention to treat. ETHICS AND DISSEMINATION: Ethics approval was provided by the Northern A Health and Disability Ethics Committee (Ministry of Health, New Zealand; 16/NTA/172). The trial results will be published in peer-reviewed journals and presented at international conferences. TRIAL REGISTRATION NUMBER: ACTRN12615001351505; Pre-results.
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Disbiosis/terapia , Trasplante de Microbiota Fecal/métodos , Microbioma Gastrointestinal , Obesidad Infantil/terapia , Adolescente , Adulto , Índice de Masa Corporal , Método Doble Ciego , Disbiosis/etiología , Heces/microbiología , Femenino , Estudios de Seguimiento , Humanos , Masculino , Obesidad Infantil/complicaciones , Calidad de Vida , Resultado del Tratamiento , Adulto JovenRESUMEN
Key Points: The microbiome has been implicated in the development of obesity. Conventional therapeutic methods have limited effectiveness for the treatment of obesity and prevention of related complications. Gut microbiome transplantation may represent an alternative and effective therapy for the treatment of obesity. Obesity has reached epidemic proportions. Despite a better understanding of the underlying pathophysiology and growing treatment options, a significant proportion of obese patients do not respond to treatment. Recently, microbes residing in the human gastrointestinal tract have been found to act as an "endocrine" organ, whose composition and functionality may contribute to the development of obesity. Therefore, fecal/gut microbiome transplantation (GMT), which involves the transfer of feces from a healthy donor to a recipient, is increasingly drawing attention as a potential treatment for obesity. Currently the evidence for GMT effectiveness in the treatment of obesity is preliminary. Here, we summarize benefits, procedures, and issues associated with GMT, with a special focus on obesity.