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A spatial gradient of bacterial diversity in the human oral cavity shaped by salivary flow.
Proctor, DM, Fukuyama, JA, Loomer, PM, Armitage, GC, Lee, SA, Davis, NM, Ryder, MI, Holmes, SP, Relman, DA
Nature communications. 2018;9(1):681
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Identifying spatial patterns in the human microbiota is necessary to provide insight into mechanisms that either maintain or disrupt its healthy state. The aim of this study was to identify the type and extent of oral spatial patterns formed by bacterial communities, as well as observe the impact of low salivary flow on the spatial patterns. Dental exams were performed on 31 participants to evaluate the oral health status and follow-up was dependent on group allocation. This study found bacterial communities were distinguishable depending on types of teeth and tissue. Further, bacteria on soft and hard tissues varied across the front and back of the oral cavity in a gradient-manner, implying that salivary flow plays a role in establishing the bacterial community gradient in the oral cavity. Based on these results, the authors recommend spatial patterns and processes be explored in other body parts to better understand health and disease.
Abstract
Spatial and temporal patterns in microbial communities provide insights into the forces that shape them, their functions and roles in health and disease. Here, we used spatial and ecological statistics to analyze the role that saliva plays in structuring bacterial communities of the human mouth using >9000 dental and mucosal samples. We show that regardless of tissue type (teeth, alveolar mucosa, keratinized gingiva, or buccal mucosa), surface-associated bacterial communities vary along an ecological gradient from the front to the back of the mouth, and that on exposed tooth surfaces, the gradient is pronounced on lingual compared to buccal surfaces. Furthermore, our data suggest that this gradient is attenuated in individuals with low salivary flow due to Sjögren's syndrome. Taken together, our findings imply that salivary flow influences the spatial organization of microbial communities and that biogeographical patterns may be useful for understanding host physiological processes and for predicting disease.
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Profiling of lung microbiota in the patients with obstructive sleep apnea.
Lu, D, Yao, X, Abulimiti, A, Cai, L, Zhou, L, Hong, J, Li, N
Medicine. 2018;97(26):e11175
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Obstructive sleep apnoea is a disease of lower airways of the lungs. Numerous studies have reported that various commensal bacteria such as Streptococcus, Veillonella, Prevotella, and Actinomyces are predominant in healthy human lungs. Therefore the current study was designed to analyse and assess the lower airway microbiota in patients with Obstructive sleep apnoea (OSA) and compared it to that of control group (who did not have OSA but had other lung disease). Sleep apnoea was examined with a sleep diagnostic device and data were analysed with Profusion PSG software. The study was conducted in China and total number of subjects who took part in the study was 19. On comparison between the two groups revealed that, Fusobacteria species of bacteria was higher in OSA patients whilst firmicutes species was significantly less. The result from the study indicated that lung microbiota in OSA patients were different from those of control group(non OSA )patients and maybe manipulation of the microbiota could be considered as an intervention to increase airway immunity and decrease susceptibility to airway infections. Though the authors concluded that more studies are needed before these findings and interventions can be confirmed.
Abstract
Lung microbiota may affect innate immunity and treatment consequence in the obstructive sleep apnea (OSA) patients. Bronchoalveolar lavage fluid (BALF) was obtained from 11 OSA patients and 8 patients with other lung diseases as control, and used for lung microbiota profiling by PCR amplification and sequencing of the microbial samples. It was demonstrated that phyla of Firmicutes, Fusobacteria, and Bacteriodetes were relatively abundant in the lung microbiota. Alpha-diversity comparison between OSA and control group revealed that Proteobacteria and Fusobacteria were significantly higher in OSA patients (0.3863 ± 0.0631 and 0.0682 ± 0.0159, respectively) than that in control group (0.119 ± 0.074 and 0.0006 ± 0.0187, respectively, P < .05 for both phyla). In contrast, Firmicutes was significantly less in OSA patients (0.1371 ± 0.0394) compared with that in the control group (0.384 ± 0.046, P < .05). Comparison within a group (ß-diversity) indicated that the top 5 phyla in the OSA lung were Proteobacteria, Bacteroidetes, Firmicutes, Fusobacteria, and Acidobacteria, while the top 5 phyla in the control group were Firmicutes, Bacteroidetes, Proteobacteria, Actinobacteria, and Acidobacteria. These findings indicated that lung microbiota in OSA is distinct from that of non-OSA patients. Manipulation of the microbiota may be an alternative strategy to augment airway immunity and to reduce susceptibility to airway infection.
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Self-reported bovine milk intake is associated with oral microbiota composition.
Johansson, I, Esberg, A, Eriksson, L, Haworth, S, Lif Holgerson, P
PloS one. 2018;13(3):e0193504
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Dietary bovine milk consumption has been associated with both positive and negative health effects. The aim of this study was to explore the association between bovine milk intake and oral microbiota profile. Saliva and tooth biofilm samples were obtained from 154 Swedish adolescents and food frequency questionnaires were completed. A replication cohort of 31,571 was also studied to find patterns in diet intake, lifestyle factors and dental caries. The primary finding of this study was that bovine milk consumption can modulate oral microbiota, and that low milk intake was associated with higher prevalence of opportunistic bacteria. Interestingly there was no association between milk intake and dental caries, highlighting the complexity of this disease. Based on these results, the authors hypothesise milk consumption may also produce similar effects in the gut microbiome.
Abstract
Bovine milk intake has been associated with various disease outcomes, with modulation of the gastro-intestinal microbiome being suggested as one potential mechanism. The aim of the present study was to explore the oral microbiota in relation to variation in self-reported milk intake. Saliva and tooth biofilm microbiota was characterized by 16S rDNA sequencing, PCR and cultivation in 154 Swedish adolescents, and information on diet and other lifestyle markers were obtained from a questionnaire, and dental caries from clinical examination. A replication cohort of 31,571 adults with similar information on diet intake, other lifestyle markers and caries was also studied. Multivariate partial least squares (PLS) modelling separated adolescents with low milk intake (lowest tertile with <0.4 servings/day) apart from those with high intake of milk (≥3.7 servings/day) based on saliva and tooth biofilm, respectively. Taxa in several genera contributed to this separation, and milk intake was inversely associated with the caries causing Streptococcus mutans in saliva and tooth biofilm samples by sequencing, PCR and cultivation. Despite the difference in S. mutans colonization, caries prevalence did not differ between milk consumption groups in the adolescents or the adults in the replication cohort, which may reflect that a significant positive association between intake of milk and sweet products was present in both the study and replication group. It was concluded that high milk intake correlates with different oral microbiota and it is hypothesized that milk may confer similar effects in the gut. The study also illustrated that reduction of one single disease associated bacterial species, such as S. mutans by milk intake, may modulate but not prevent development of complex diseases, such as caries, due to adverse effects from other causal factors, such as sugar intake in the present study.
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A lecithin phosphatidylserine and phosphatidic acid complex (PAS) reduces symptoms of the premenstrual syndrome (PMS): Results of a randomized, placebo-controlled, double-blind clinical trial.
Schmidt, K, Weber, N, Steiner, M, Meyer, N, Dubberke, A, Rutenberg, D, Hellhammer, J
Clinical nutrition ESPEN. 2018;24:22-30
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PMS is characterized by a cluster of somatic and psychological symptoms of varying severity. These symptoms occur only during the luteal phase of the menstrual cycle and resolve during the first days of menses. Recent observational data suggest that supplementation with Lipogen's phosphatidylserine and phosphatidic acid complex (PAS) alleviates these PMS symptoms. The aim of this study was to observe the effects of PAS on PMS symptom severity. This study is a prospective, randomised, placebo-controlled, double-blind single centre study with two arms (PAS or placebo). Participants were randomly assigned to one of the two groups. Results show beneficial effects of a daily intake of PAS over 3 cycles on symptom levels as assessed by several well-recognized instruments for PMS evaluation. The PAS complex alleviated the PMS symptoms, providing a safe alternative to standard pharmacological treatment. Authors conclude that their findings merit consideration of developing the PAS complex as a botanical drug for treatment of PMS symptoms.
Abstract
BACKGROUND & AIMS Many women experience emotional and physical symptoms around the time of ovulation and more so before menstruation interfering with their daily normal life also known as premenstrual syndrome (PMS). Recent observational data suggest that supplementation with Lipogen's phosphatidylserine (PS) and phosphatidic acid (PA) complex (PAS) alleviates these PMS symptoms. The aim of this study was to confirm these observations on the effects of PAS on PMS symptom severity within a controlled clinical trial setting. METHODS Forty women aged 18-45 years with a diagnosis of PMS were assigned to either take PAS (containing 400 mg PS & 400 mg PA per day) or a matching placebo. The study comprised 5 on-site visits including 1 baseline menstrual cycle followed by 3 treatment cycles. Treatment intake was controlled for by using an electronic device, the Medication Event Monitoring System (MEMS®). Primary outcome of the study was the PMS symptoms severity as assessed by using the Daily Record of Severity of Problems (DRSP). Further, SIPS questionnaire (a German version of the Premenstrual Symptoms Screening Tool (PSST)), salivary hormone levels (cortisol awakening response (CAR) and evening cortisol levels) as well as serum levels (cortisol, estradiol, progesterone and corticosteroid binding globulin (CBG)) were assessed. RESULTS PMS symptoms as assessed by the DRSP Total score showed a significantly better improvement (p = 0.001) over a 3 cycles PAS intake as compared to placebo. In addition, PAS treated women reported a greater improvement in physical (p = 0.002) and depressive symptoms (p = 0.068). They also reported a lower reduction of productivity (p = 0.052) and a stronger decrease in interference with relationships with others (p = 0.099) compared to the placebo group. No other DRSP scale or item showed significant results. Likewise, the reduction in the number of subjects fulfilling PMS or premenstrual dysphoric disorder (PMDD) criteria as classified by the SIPS did not differ between the PAS and the placebo group. For the biomarkers, the salivary cortisol percentage increase of the CAR was significantly less pronounced in the follicular phase of cycle 4 than in the follicular phase of cycle 1 for subjects taking PAS when compared to subjects taking placebo (p = 0.018). Furthermore, the change of serum cortisol levels between visit 1 and visit 5 differed significantly between groups (p = 0.043). While serum cortisol levels of PAS treated females slightly decreased between visit 1 and visit 5, cortisol levels of females treated with placebo increased. For all other biomarkers, no treatment effects were observed over the 4 cycles study period. Overall, this study confirms that a daily intake of PAS, containing 400 mg PS and 400 mg PA, can be considered as safe. CONCLUSIONS Results substantiate the efficacy of PAS in reducing symptoms of PMS. In view of the recent inclusion of severe PMS symptoms (PMDD) in the fifth edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-5), the positive results of this clinical study merits consideration of developing the PAS complex as a botanical drug for treatment of PMDD. CLINICAL TRIAL REGISTRATION The study is registered at Deutsches Register Klinischer Studien with the registration number DRKS00009005.
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Impact of Experimentally Induced Cognitive Dietary Restraint on Eating Behavior Traits, Appetite Sensations, and Markers of Stress during Energy Restriction in Overweight/Obese Women.
Morin, I, Bégin, C, Maltais-Giguère, J, Bédard, A, Tchernof, A, Lemieux, S
Journal of obesity. 2018;2018:4259389
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The treatment of obesity has become a public health priority given the negative impact of this condition on physical and mental health. The aim of this study was to compare the effects of energy restriction alone or in combination with induced cognitive dietary restraint (CDR) on eating behaviour traits, appetite sensations, and markers of stress in overweight and obese premenopausal women. The study is a single-blinded randomised clinical study which recruited premenopausal women aged between 26 and 50 years. The participants were randomised to either an energy-restriction-plus-induced CDR condition (CDR+group) or an energy-restriction-without induced CDR condition (CDR−group). Results indicate that inducing CDR in a context of energy restriction had no further effects on eating behaviour traits, appetite sensations, and markers of stress in the short term as well as in the longer term than energy restriction alone. Authors conclude that increasing CDR has no negative impact on factors regulating energy balance in the context of energy restriction.
Abstract
Weight loss has been associated with changes in eating behaviors and appetite sensations that favor a regain in body weight. Since traditional weight loss approaches emphasize the importance of increasing cognitive dietary restraint (CDR) to achieve negative energy imbalance, it is difficult to untangle the respective contributions of energy restriction and increases in CDR on factors that can eventually lead to body weight regain. The present study aimed at comparing the effects of energy restriction alone or in combination with experimentally induced CDR on eating behavior traits, appetite sensations, and markers of stress in overweight and obese women. We hypothesized that the combination of energy restriction and induced CDR would lead to more prevalent food cravings, increased appetite sensations, and higher cortisol concentrations than when energy restriction is not coupled with induced CDR. A total of 60 premenopausal women (mean BMI: 32.0 kg/m2; mean age: 39.4 y) were provided with a low energy density diet corresponding to 85% of their energy needs during a 4-week fully controlled period. At the same time, women were randomized to either a condition inducing an increase in CDR (CDR+ group) or a condition in which CDR was not induced (CRD- group). Eating behavior traits (Three-Factor Eating Questionnaire and Food Craving Questionnaire), appetite sensations (after standardized breakfast), and markers of stress (Perceived Stress Scale; postawakening salivary cortisol) were measured before (T = 0 week) and after (T = 4 weeks) the 4-week energy restriction, as well as 3 months later. There was an increase in CDR in the CDR+ group while no such change was observed in the CDR- group (p=0.0037). No between-group differences were observed for disinhibition, hunger, cravings, appetite sensations, perceived stress, and cortisol concentrations. These results suggest that a slight increase in CDR has no negative impact on factors regulating energy balance in the context of energy restriction.
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Short-Term Exercise Training Inconsistently Influences Basal Testosterone in Older Men: A Systematic Review and Meta-Analysis.
Hayes, LD, Elliott, BT
Frontiers in physiology. 2018;9:1878
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The levels of testosterone decrease as men age and is associated with accelerated ageing. Approaches to increase testosterone levels may therefore be of benefit. There are complications with administering testosterone and so exercise has been proposed as a non-pharmacological intervention to increase serum testosterone in older males. The purpose of this review and meta-analysis was to look at suitable studies linking exercise and testosterone levels in older males and to see whether types of exercise (endurance, resistance and interval training) made a difference. There is a belief that resistance exercise increases basal testosterone over time. However, this was not observed in this meta-analysis. HIIT (high intensity interval training), and endurance training showed the most promise for increasing basal testosterone in older men. There is a need for more studies to improve the quality of available evidence and at present, exercise is probably the best non-pharmacological countermeasure to loss of muscle function with human aging.
Abstract
Background: The age-associated decrease in testosterone is one mechanism suggested to accelerate the aging process in males. Therefore, approaches to increase endogenous testosterone may be of benefit. The aim of this paper was to undertake a Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA)-accordant meta-analysis concerning the effect of exercise on total (TT), bioavailable (bio-T), free (free-T), and salivary (sal-T) testosterone in older males. Methods: Databases were searched up to and including 20th February 2018 for the terms "testosterone AND exercise AND aging AND males," "testosterone AND exercise AND old AND males," "testosterone AND training AND aging AND males," and "testosterone AND training AND old AND males". From 1259 originally identified titles, 22 studies (randomized controlled trials; RCTs; n = 9, and uncontrolled trials; UCTs; n = 13) were included which had a training component, participants ≥60 years of age, and salivary or serum testosterone as an outcome measure. Meta-analyses were conducted on change to testosterone following training using standardized difference in means (SDM) and random effects models. Results: The overall SDM for endurance training, resistance training, and interval training was 0.398 (95% CI = 0.034-0.761; P = 0.010), -0.003 (95% CI = -0.330-0.324; P = 0.986), and 0.283 (95% CI = 0.030-0.535; P = 0.028), respectively. Resistance training exhibited a qualitative effect of hormone fraction whereby free-T resulted in the greatest SDM (0.253; 95% CI = -0.043-0.549; P = 0.094), followed by TT (0.028; 95% CI = -0.204-0.260; P = 0.813), and resistance training negatively influenced bio-T (-0.373; 95% CI = -0.789-0.042; P = 0.078). Due to the small number of studies, subgroup analysis was not possible for endurance training and interval training studies. Conclusions: Data from the present investigation suggests that resistance training does not significantly influence basal testosterone in older men. Magnitude of effect was influenced by hormone fraction, even within the same investigation. Aerobic training and interval training did result in small, significant increases in basal testosterone. The magnitude of effect is small but the existing data are encouraging and may be an avenue for further research.
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Bifidobacterium bifidum YIT 10347 fermented milk exerts beneficial effects on gastrointestinal discomfort and symptoms in healthy adults: A double-blind, randomized, placebo-controlled study.
Gomi, A, Yamaji, K, Watanabe, O, Yoshioka, M, Miyazaki, K, Iwama, Y, Urita, Y
Journal of dairy science. 2018;101(6):4830-4841
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Probiotics have been found to have beneficial effects in adults with functional gastrointestinal (GI) disorders, however little evidence exists regarding its effects on healthy adults. The aim of this prospective, randomised, double-blind, placebo-controlled, parallel-group trial was to clarify the beneficial effects of Bifidobacterium bifidum (B bifidum) on gastric symptoms in 100 healthy Japanese adults who experience temporary GI symptoms. Participants were randomised to consume active fermented milk or placebo milk matched for colour, taste and packaging daily for four weeks and various qualitative and quantitative measurements were assessed. This trial found the group consuming B bifidum experienced significantly better relief from upper GI symptoms compared with the placebo group. These findings suggest daily consumption of milk fermented with B bifidum helps relive GI discomfort and symptoms in healthy adults with no risk of side effects. Based on these results, the authors conclude fermented milk drinks can be recommended to patients who experience temporary GI pain.
Abstract
In a preliminary open-label trial by our group, Bifidobacterium bifidum YIT 10347 (YIT10347) relieved gastric symptoms in patients with functional gastrointestinal disorders. Hence, in this study, we investigated the effects of YIT10347 on gastrointestinal symptoms in healthy adults. In this prospective double-blind, randomized, placebo-controlled trial (UMIN000024654), 100 healthy Japanese adults were randomly assigned to a YIT10347 group or placebo group and consumed 100 mL of YIT10347-fermented milk or placebo fermented milk, respectively, every day for 4 wk. Gastrointestinal symptoms were evaluated by using the modified Frequency Scale for Symptoms of Gastroesophageal Reflux Disease (m-FSSG) and Gastrointestinal Symptom Rating Scale (GSRS) as primary endpoints. Mental symptoms, quality of life, salivary stress markers, and gastric emptying were evaluated as secondary endpoints. Effectiveness and safety were analyzed in a per-protocol set (YIT10347 group, n = 39; placebo group, n = 40) and full analysis set (YIT10347 group, n = 50; placebo group, n = 50), respectively. In the m-FSSG evaluation, the YIT10347 group had a significantly higher relief rate of postprandial discomfort and greater changes in postprandial epigastric pain score from baseline than the placebo group. In the GSRS evaluation, the YIT10347 group had significantly higher relief rates of overall gastrointestinal symptoms, upper gastrointestinal symptoms, flatus, and diarrhea than the placebo group. We detected no significant differences in scores or relief rates of mental symptoms and quality of life, a salivary stress marker, or gastric emptying between the 2 groups. No severe adverse events associated with test beverage consumption were observed in either group. These findings suggest that daily consumption of YIT10347-fermented milk exerts beneficial effects on gastrointestinal discomfort and symptoms such as postprandial discomfort and epigastric pain in healthy adults.
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A sympathetic nervous system evaluation of obesity stigma.
Oliver, MD, Datta, S, Baldwin, DR
PloS one. 2017;12(10):e0185703
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The negative health consequences of obesity are well known. Those classified as obese also suffer from discrimination which has further negative psychological and physiological effects on well-being. The aim of this study was to see if attitudes to obesity can be modified at the physiological and psychological level by priming. 70 people aged 18-53 were randomly assigned to 2 groups. One group was shown images of obesity in negative settings, the other in positive settings. All participants then viewed an actual obesity discrimination incident. Levels of the digestive enzyme salivary alpha amylase (sAA) and skin conductance (SC) were taken as measures of sympathetic nervous system (SNS) activity. Individuals in the negative priming group had significantly more SC arousal and exhibited the highest overall sAA response after viewing the incident when compared to the positively primed group. The authors conclude that clinicians addressing stigma issues should consider the use of positively primed images as a method for reducing the possible long-term physiological consequences of the negative attitudes surrounding obesity.
Abstract
The portrayal of obesity in the media is often one of negativity. Consequently, it may generate an increase in stigma. Obesity stigma, a form of social discrimination, is responsible for many of the negative psychological and physiological effects on individual wellness. These effects not only impact individual health, but also affect the economy, and ultimately, societal wellness. In an attempt to examine the influence of the media on obesity stigma, this study tested the hypothesis that positive priming would lead to a reduction in obesity stigma. To further our understanding of this relationship, we: 1) examined the role of priming on physiological measures (e.g. salivary alpha amylase and skin conductance) in 70 college students by introducing positive and negative media images of individuals with obesity, and 2) assessed psychological measures (e.g. perceived stress, need to belong, and self-esteem, and Body Mass Index). After the priming manipulation, participants read a vignette depicting the discrimination of an individual with obesity and answered subsequent questions assessing participants' attributional blame of obesity. Results of this study revealed that priming affects physiological responding to obesity stigmatization. In conclusion, these findings suggest that incorporating positive media images of individuals with obesity may be an effective tool for reducing stigma and the various physiological consequences associated with it, which in turn, can enhance societal health and wellness.
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Substituting whole grains for refined grains in a 6-wk randomized trial has a modest effect on gut microbiota and immune and inflammatory markers of healthy adults.
Vanegas, SM, Meydani, M, Barnett, JB, Goldin, B, Kane, A, Rasmussen, H, Brown, C, Vangay, P, Knights, D, Jonnalagadda, S, et al
The American journal of clinical nutrition. 2017;105(3):635-650
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Increased whole grain consumption has been associated with reduced levels of inflammation. This randomised, controlled trial aimed to assess the effects of a whole grain diet in comparison with a refined grain diet on the immune system, levels of inflammation and gut bacteria. 81 men and women aged between 40 and 60 were randomly assigned to either a whole grain or a refined grain diet for a period of 6 weeks. All other dietary components were kept the same and calorie levels were controlled to maintain weight levels. The study findings showed a positive effect on stool frequency and stool weight with the whole grain diet in comparison to the refined grain diet. The whole grain diet also showed modest positive effects on gut bacteria profiles and aspects of immunity. The whole grain diet showed no effects on markers of inflammation.
Abstract
Background: Observational studies suggest an inverse association between whole-grain (WG) consumption and inflammation. However, evidence from interventional studies is limited, and few studies have included measurements of cell-mediated immunity.Objective: We assessed the effects of diets rich in WGs compared with refined grains (RGs) on immune and inflammatory responses, gut microbiota, and microbial products in healthy adults while maintaining subject body weights.Design: After a 2-wk provided-food run-in period of consuming a Western-style diet, 49 men and 32 postmenopausal women [age range: 40-65 y, body mass index (in kg/m2) <35] were assigned to consume 1 of 2 provided-food weight-maintenance diets for 6 wk.Results: Compared with the RG group, the WG group had increased plasma total alkyresorcinols (a measure of WG intake) (P < 0.0001), stool weight (P < 0.0001), stool frequency (P = 0.02), and short-chain fatty acid (SCFA) producer Lachnospira [false-discovery rate (FDR)-corrected P = 0.25] but decreased pro-inflammatory Enterobacteriaceae (FDR-corrected P = 0.25). Changes in stool acetate (P = 0.02) and total SCFAs (P = 0.05) were higher in the WG group than in the RG group. A positive association was shown between Lachnospira and acetate (FDR-corrected P = 0.002) or butyrate (FDR-corrected P = 0.005). We also showed that there was a higher percentage of terminal effector memory T cells (P = 0.03) and LPS-stimulated ex vivo production of tumor necrosis factor-α (P = 0.04) in the WG group than in the RG group, which were positively associated with plasma alkylresorcinol concentrations.Conclusion: The short-term consumption of WGs in a weight-maintenance diet increases stool weight and frequency and has modest positive effects on gut microbiota, SCFAs, effector memory T cells, and the acute innate immune response and no effect on other markers of cell-mediated immunity or systemic and gut inflammation. This trial was registered at clinicaltrials.gov as NCT01902394.
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The Effect of Mitochondrial Supplements on Mitochondrial Activity in Children with Autism Spectrum Disorder.
Delhey, LM, Nur Kilinc, E, Yin, L, Slattery, JC, Tippett, ML, Rose, S, Bennuri, SC, Kahler, SG, Damle, S, Legido, A, et al
Journal of clinical medicine. 2017;6(2)
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Primary mitochondrial disease and secondary mitochondria disorders have received increasing recognition in the medical world. In fact, mitochondrial dysfunction plays a significant role in many common illnesses such as diabetes, obesity, cancer and heart disease, as well as neurologic and psychiatric conditions. Yet less is known about the optimal treatment for mitochondrial disorders. Given the scarcity of clinical research, current treatment is mostly based on expert opinions, preclinical trials and animal models. Autism spectrum disorder (ASD) is a neurological and developmental condition that manifests in divergent behaviours affecting learning, communication and social engagement. Recent research suggests that there may be a link between mitochondrial abnormalities and ASD. About half of children with ASD display measurable biomarkers indicative of mitochondrial dysfunction, and the prevalence of primary mitochondrial disorders is much higher in children with ASD compared to those without ASD presentation. Several mitochondrial co-factors are supplemented in the management of mitochondria disease and also have shown promising effects on ASD symptoms. Hence this observational study sought to explore the impact of such substances on mitochondrial function in children with ASD. The project involved 127 children with ASD, some subjects were on specific mitochondrial supplements and some also had a diagnosed mitochondrial disease. The activity of mitochondrial metabolism was assessed at several stages, via a salivary mouth swab. Results from this study suggested that several common mitochondrial supplements such as fatty acids, antioxidants, B12 and folate influence mitochondrial function. However, some of these influences were more pronounced or in some cases limited to the subgroup that also had prevailing mitochondrial disease. The findings affirm that these interventions improve mitochondrial function and maybe be most effective in ASD cases with underlying metabolic disorders.
Abstract
Treatment for mitochondrial dysfunction is typically guided by expert opinion with a paucity of empirical evidence of the effect of treatment on mitochondrial activity. We examined citrate synthase and Complex I and IV activities using a validated buccal swab method in 127 children with autism spectrum disorder with and without mitochondrial disease, a portion of which were on common mitochondrial supplements. Mixed-model linear regression determined whether specific supplements altered the absolute mitochondrial activity as well as the relationship between the activities of mitochondrial components. Complex I activity was increased by fatty acid and folate supplementation, but folate only effected those with mitochondrial disease. Citrate synthase activity was increased by antioxidant supplementation but only for the mitochondrial disease subgroup. The relationship between Complex I and IV was modulated by folate while the relationship between Complex I and Citrate Synthase was modulated by both folate and B12. This study provides empirical support for common mitochondrial treatments and demonstrates that the relationship between activities of mitochondrial components might be a marker to follow in addition to absolute activities. Measurements of mitochondrial activity that can be practically repeated over time may be very useful to monitor the biochemical effects of treatments.