Diet Can Impact Microbiota Composition in Children With Autism Spectrum Disorder

Diet is one of the most influential environmental factors in determining the composition of the gastrointestinal microbiota. Microbial dysbiosis in children with Autism Spectrum Disorder (ASD) and the impact of some bacterial taxa on symptoms of ASD has been recognized. Children with ASD are often described as picky eaters with low intake of fiber-rich foods, including fruits and vegetables. However, the impact of diet on the microbiota composition in children with ASD is largely unknown. Herein, fecal samples, 3 day food diaries and the Youth and Adolescence Food Frequency questionnaire (YAQ) were collected from children with ASD (ASD; n = 26) and unaffected controls (CONT; n = 32). Children's ASD symptoms were determined using the Pervasive Developmental Disorder Behavior Inventory Screening Version (PDDBI-SV). Differences in the microbiota composition at the phyla, order, family, and genus level between ASD and CONT were observed. Microbiota composition of children with ASD was investigated in relation to feeding behavior, nutrient and food group intake as well as dietary patterns derived from the YAQ. In children with ASD, two distinct dietary patterns (DP) were associated with unique microbial profiles. DP1, characterized by higher intakes of vegetables, legumes, nuts and seeds, fruit, refined carbohydrates, and starchy vegetables, but lower intakes of sweets, was associated with lower abundance of Enterobacteriaceae, Lactococcus, Roseburia, Leuconostoc, and Ruminococcus. DP2, characterized by low intakes of vegetables, legumes, nuts and seeds and starchy vegetables, was associated with higher Barnesiellaceae and Alistipes and lower Streptophyta, as well as higher levels of propionate, isobutyrate, valerate, and isovalerate. Peptostreptococcaceae and Faecalibacterium predicted social deficit scores in children with ASD as measured by the PDDBI-SV. Diet-associated microbial profiles were related to GI symptoms, but no significant interaction between nutrition and microbiota in predicting social deficit scores were observed. In conclusion, dietary patterns associated with fecal microbiota composition and VFA concentrations in children with ASD were identified. Future studies using a larger sample size and measuring other behaviors associated with ASD are needed to investigate whether dietary intake may be a modifiable moderator of ASD symptoms

Metabolomic workflow for the accurate and high-throughput exploration of the pathways of tryptophan, tyrosine, phenylalanine, and branched-chain amino acids in human biofluids

10openInternationalInternational coauthor/editorThe modulation of host and dietary metabolites by gut microbiota (GM) is important for maintaining correct host physiology and in the onset of various pathologies. An ultrahigh-performance liquid chromatography-electrospray ionization-tandem mass spectrometry method was developed for the targeted quantitation in human plasma, serum, and urine of 89 metabolites resulting from human-GM cometabolism of dietary essential amino acids tryptophan, tyrosine, and phenylalanine as well as branched-chain amino acids. Ninety-six-well plate hybrid-SPE enables fast clean-up of plasma and serum. Urine was diluted and filtered. A 15 min cycle enabled the acquisition of 96 samples per day, with most of the metabolites stable in aqueous solution for up to 72 h. Calibration curves were specifically optimized to cover expected concentrations in biological fluids, and limits of detection were at the order of ppb. Matrix effects were in acceptable ranges, and analytical recoveries were in general greater than 80%. Inter and intraday precision and accuracy were satisfactory. We demonstrated its application in plasma and urine samples obtained from the same individual in the frame of an interventional study, allowing the quantitation of 51 metabolites. The method could be considered the reference for deciphering changes in human-gut microbial cometabolism in health and disease. Data are available via Metabolights with the identifier MTBLS4399.openAnesi, Andrea; Berding, Kirsten; Clarke, Gerard; Stanton, Catherine; Cryan, John F.; Caplice, Noel; Ross, R. Paul; Doolan, Andrea; Vrhovsek, Urska; Mattivi, FulvioAnesi, A.; Berding, K.; Clarke, G.; Stanton, C.; Cryan, J.F.; Caplice, N.; Ross, R.P.; Doolan, A.; Vrhovsek, U.; Mattivi, F

Acute stress increases monocyte levels and modulates receptor expression in healthy females

There has been a growing recognition of the involvement of the immune system in stress-related disorders. Acute stress leads to the activation of neuroendocrine systems, which in turn orchestrate a large-scale redistribution of innate immune cells, such as monocytes. Even though acute stress/monocyte interactions have been wellcharacterized in mice, this is not the case for humans. As such, this study aimed to investigate whether acute stress modulates blood monocyte levels in a subtype-dependent manner and whether the receptor expression of stress-related receptors is affected in humans. Blood was collected from healthy female volunteers at baseline and 1 h after the socially evaluated cold pressor test, after which blood monocyte levels and receptor expression were assessed by flow cytometry. Our results reveal a stress-induced increase in blood monocyte levels, which was independent of monocyte subtypes. Furthermore, colony stimulating factor 1 receptor (CSF-1R) and CD29 receptor expression was increased, while CD62L showed a trend towards increased expression. These results provide novel insights into how acute stress affects the innate immune system

Recipe for a Healthy Gut: Intake of Unpasteurised Milk Is Associated with Increased Lactobacillus Abundance in the Human Gut Microbiome

peer-reviewedIntroduction: The gut microbiota plays a role in gut–brain communication and can influence psychological functioning. Diet is one of the major determinants of gut microbiota composition. The impact of unpasteurised dairy products on the microbiota is unknown. In this observational study, we investigated the effect of a dietary change involving intake of unpasteurised dairy on gut microbiome composition and psychological status in participants undertaking a residential 12-week cookery course on an organic farm. Methods: Twenty-four participants completed the study. The majority of food consumed during their stay originated from the organic farm itself and included unpasteurised milk and dairy products. At the beginning and end of the course, participants provided faecal samples and completed self-report questionnaires on a variety of parameters including mood, anxiety and sleep. Nutrient intake was monitored with a food frequency questionnaire. Gut microbiota analysis was performed with 16S rRNA gene sequencing. Additionally, faecal short chain fatty acids (SCFAs) were measured. Results: Relative abundance of the genus Lactobacillus increased significantly between pre- and post-course time points. This increase was associated with participants intake of unpasteurised milk and dairy products. An increase in the faecal SCFA, valerate, was observed along with an increase in the functional richness of the microbiome profile, as determined by measuring the predictive neuroactive potential using a gut–brain module approach. Conclusions: While concerns in relation to safety need to be considered, intake of unpasteurised milk and dairy products appear to be associated with the growth of the probiotic bacterial genus, Lactobacillus, in the human gut. More research is needed on the effect of dietary changes on gut microbiome composition, in particular in relation to the promotion of bacterial genera, such as Lactobacillus, which are recognised as being beneficial for a range of physical and mental health outcomes

Altered stress responses in adults born by Caesarean section

peer-reviewedBirth by Caesarean-section (C-section), which increases the risk for metabolic and immune disorders, disrupts the normal initial microbial colonisation of the gut, in addition to preventing early priming of the stress and immune-systems.. Animal studies have shown there are enduring psychological processes in C-section born mice. However, the long-term impact of microbiota-gut-brain axis disruptions due to birth by C-section on psychological processes in humans is unknown. Forty age matched healthy young male university students born vaginally and 36 C-section delivered male students were recruited. Participants underwent an acute stressor, the Trier social stress test (TSST), during a term-time study visit. A subset of participants also completed a study visit during the university exam period, representing a naturalistic stressor. Participants completed a battery of cognitive tests and self-report measures assessing mood, anxiety, and perceived stress. Saliva, blood, and stool samples were collected for analysis of cortisol, peripheral immune profile, and the gut microbiota. Young adults born by C-section exhibit increased psychological vulnerability to acute stress and a prolonged period of exam-related stress. They did not exhibit an altered salivary cortisol awakening response to the TSST, but their measures of positive affect were significantly lower than controls throughout the procedure. Both C-section and vaginally-delivered participants performed equally well on cognitive assessments. Most of the initial effects of delivery mode on the gut microbiome did not persist into adulthood as the gut microbiota profile showed modest changes in composition in adult vaginally-delivered and C-sectioned delivered subjects. From an immune perspective, concentrations of IL-1β and 1L-10 were higher in C-section participants. These data confirm that there is a potential enduring effect of delivery mode on the psychological responses to acute stress during early adulthood. The mental health implications of these observations require further study regarding policies on C-section use

Multi-level analysis of the gut-brain axis shows autism spectrum disorder-associated molecular and microbial profiles

Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by heterogeneous cognitive, behavioral and communication impairments. Disruption of the gut-brain axis (GBA) has been implicated in ASD although with limited reproducibility across studies. In this study, we developed a Bayesian differential ranking algorithm to identify ASD-associated molecular and taxa profiles across 10 cross-sectional microbiome datasets and 15 other datasets, including dietary patterns, metabolomics, cytokine profiles and human brain gene expression profiles. We found a functional architecture along the GBA that correlates with heterogeneity of ASD phenotypes, and it is characterized by ASD-associated amino acid, carbohydrate and lipid profiles predominantly encoded by microbial species in the genera Prevotella, Bifidobacterium, Desulfovibrio and Bacteroides and correlates with brain gene expression changes, restrictive dietary patterns and pro-inflammatory cytokine profiles. The functional architecture revealed in age-matched and sex-matched cohorts is not present in sibling-matched cohorts. We also show a strong association between temporal changes in microbiome composition and ASD phenotypes. In summary, we propose a framework to leverage multi-omic datasets from well-defined cohorts and investigate how the GBA influences ASD

Bifidobacterium longum counters the effects of obesity: Partial successful translation from rodent to human

peer-reviewedBackgroundThe human gut microbiota has emerged as a key factor in the development of obesity. Certain probiotic strains have shown anti-obesity effects. The objective of this study was to investigate whether Bifidobacterium longum APC1472 has anti-obesity effects in high-fat diet (HFD)-induced obese mice and whether B. longum APC1472 supplementation reduces body-mass index (BMI) in healthy overweight/obese individuals as the primary outcome. B. longum APC1472 effects on waist-to-hip ratio (W/H ratio) and on obesity-associated plasma biomarkers were analysed as secondary outcomes. MethodsB. longum APC1472 was administered to HFD-fed C57BL/6 mice in drinking water for 16 weeks. In the human intervention trial, participants received B. longum APC1472 or placebo supplementation for 12 weeks, during which primary and secondary outcomes were measured at the beginning and end of the intervention. FindingsB. longum APC1472 supplementation was associated with decreased bodyweight, fat depots accumulation and increased glucose tolerance in HFD-fed mice. While, in healthy overweight/obese adults, the supplementation of B. longum APC1472 strain did not change primary outcomes of BMI (0.03, 95% CI [-0.4, 0.3]) or W/H ratio (0.003, 95% CI [-0.01, 0.01]), a positive effect on the secondary outcome of fasting blood glucose levels was found (-0.299, 95% CI [-0.44, -0.09]). InterpretationThis study shows a positive translational effect of B. longum APC1472 on fasting blood glucose from a preclinical mouse model of obesity to a human intervention study in otherwise healthy overweight and obese individuals. This highlights the promising potential of B. longum APC1472 to be developed as a valuable supplement in reducing specific markers of obesity. FundingThis research was funded in part by Science Foundation Ireland in the form of a Research Centre grant (SFI/12/RC/2273) to APC Microbiome Ireland and by a research grant from Cremo S.A

Bifidobacterium longum counters the effects of obesity: partial successful translation from rodent to human

The human gut microbiota has emerged as a key factor in the development of obesity. Certain probiotic strains have shown anti-obesity effects. The objective of this study was to investigate whether Bifidobacterium longum APC1472 has anti-obesity effects in high-fat diet (HFD)-induced obese mice and whether B. longum APC1472 supplementation reduces body-mass index (BMI) in healthy overweight/obese individuals as the primary outcome. B. longum APC1472 effects on waist-to-hip ratio (W/H ratio) and on obesity-associated plasma biomarkers were analysed as secondary outcomes. B. longum APC1472 was administered to HFD-fed C57BL/6 mice in drinking water for 16 weeks. In the human intervention trial, participants received B. longum APC1472 or placebo supplementation for 12 weeks, during which primary and secondary outcomes were measured at the beginning and end of the intervention. B. longum APC1472 supplementation was associated with decreased bodyweight, fat depots accumulation and increased glucose tolerance in HFD-fed mice. While, in healthy overweight/obese adults, the supplementation of B. longum APC1472 strain did not change primary outcomes of BMI (0.03, 95% CI [-0.4, 0.3]) or W/H ratio (0.003, 95% CI [-0.01, 0.01]), a positive effect on the secondary outcome of fasting blood glucose levels was found (-0.299, 95% CI [-0.44, -0.09]). This study shows a positive translational effect of B. longum APC1472 on fasting blood glucose from a preclinical mouse model of obesity to a human intervention study in otherwise healthy overweight and obese individuals. This highlights the promising potential of B. longum APC1472 to be developed as a valuable supplement in reducing specific markers of obesity. This research was funded in part by Science Foundation Ireland in the form of a Research Centre grant (SFI/12/RC/2273) to APC Microbiome Ireland and by a research grant from Cremo S.A

Nutrition and the GI microbiota in children with autism spectrum disorder and impact on symptom severity

The gastrointestinal (GI) microbiota is increasingly recognized for its ability to influence brain function and behavior. In children with Autism Spectrum Disorder (ASD), a microbial dysbiosis has been described and some bacterial taxa were found to predict certain symptoms of ASD. Additionally, picky eating behavior and food aversions are common in children with ASD, resulting in limited diet variety and decreased nutrient intake (e.g., fiber). Diet is one of the major determinants of the GI microbiota; however, previous studies have not systematically investigated the role of diet in shaping the GI microbiota in children with ASD. Likewise, overall microbial stability is recognized as more beneficial due to its ability to protect against pathogen invasion and maintain overall function. In children with ASD little is known about the stability of the microbiota. Therefore, the goal this dissertation research was to assess the impact of diet on the GI microbiota in children with ASD and microbial stability over a 6-month period with the following aims :1) to investigate differences in microbiota composition and volatile fatty acid (VFA) concentration between children with ASD and unaffected controls and investigate the relationship to ASD symptoms; 2) to determine the effect of long-term dietary patterns and short-term nutrient intake on the fecal microbial composition and VFA concentration in children with ASD and uncover relationships between diet, fecal microbiota, VFAs and ASD symptoms; and 3) to analyze the microbiota composition and VFA concentrations in children with ASD and unaffected controls over a 6-month period and identify dietary factors that correlate with a more stable microbial profile. Children with ASD (ASD; n=26) and age- and sex-matched unaffected controls (CONT; n=32) were recruited in the Midwest area. Fecal samples, a 3-day food diary, a food frequency questionnaire, and an online questionnaire collecting information on demographics, GI health, nutrition supplement use were collected at baseline, 6-weeks post-baseline and 6-months post baseline. ASD symptoms were assessed using the Pervasive Developmental Disorder Behavior Inventory – Screening Version (PDDBI-SV). Bacterial DNA was analyzed using 16S rRNA sequencing and quantitative Polymerase Chain Reaction. VFA concentrations were analyzed by gas chromatography. Dietary patterns were derived from the Youth and Adolescence Food Frequency Questionnaire (YAQ) using Principal Component Analysis and exploratory Factor Analysis. Nutrient intake was assessed by the Nutrition Data System for Research. All data were analyzed using SAS 9.4. Differences in microbiota composition between ASD and CONT were observed. Overall, β-diversity assessed by permutational multivariate analysis (PERMANOVA) differed (p=0.02) based on unweighted but not weighted d UniFrac. α-diversity measured as observed Operational Taxonomic Units (OTUs) tended to be higher (p=0.08) in ASD. Microbial abundances on the phyla, family, order and genera level were observed. Namely, ASD had higher levels of Firmicutes, Clostridiales, Clostridiaceae, Peptostreptococcaceae, Coriobacteriaceae, Clostridium, SMB53, Blautia, and Roseburia, but lower levels of Bacteroidetes, Streptophyta, Rikenellaceae, Butyricimonas, Butyrivibrio, Faecalibacterium, Dialister, and Bilophila compared to CONT. Furthermore, higher concentrations of acetate, propionate and butyrate were detected in ASD. Lastly, Peptostreptococcaceae and Faecalibacterium predicted social deficit (SOCDEF) scores in children with ASD as measured by the PDDBI-SV. Investigating dietary intake revealed that children with ASD consumed lower amounts of insoluble fiber, pectin, vitamin C and dairy, but consumed more snacks and sweets than unaffected children. To analyze the impact of nutrition on the GI microbiota, four analyses were utilized. First, correlation analyses revealed that nutrient and food group intake were associated with the abundance of bacterial taxa. Second, children with ASD characterized as picky eaters or having a repetitive eating pattern harbored a unique microbial composition. Third, two dietary patterns (DP) were empirically derived for children with ASD using the YAQ. DP-1, characterized by intakes of vegetables, starchy vegetables, legumes, nuts and seeds, fruit, grains, juice and dairy, was associated with lower abundance of Enterobacteriaceae, Lactococcus, Roseburia, Leuconostoc, and Ruminococcus. DP-2, characterized by intakes of fried foods, Kid’s meals, condiments, protein foods, snacks and starchy foods, was associated with higher abundance of Barnesiellaceae, Alistipes, and lower abundance of Streptophyta as well as higher concentrations of propionate, butyrate, isobutyrate, valerate, and isovalerate. Diet-induced microbial comppsition was related to some GI symptoms, but was not related to SOCDEF scores. Lastly, moderation analysis did not reveal a significant interaction between microbial taxa and dietary components in prediction SOCDEF scores. To investigate the temporal microbial stability, two additional samples collected over a 6-month period were analyzed for microbiota composition and VFA concentration. We found that overall the microbiota composition and metabolites concentration varied in children with ASD and variability in community membership negatively correlated with median SOCDEF scores. Furthermore, different bacteria taxa contributed to a stable microbiota profile in each group. Clostridiales, Ruminococcaceae, Lactococcus, Turicibacter, Dorea, and Phascolarctobacterium contributed to a more stable microbiota community in children with ASD whereas Barnesiellaceae, Adlercreutia, Faecalibacterium, Sutterella and Bilophila contributed more in to a stable microbiota in CONT children. Lastly, GI microbiota variability was related to habitual dietary patterns. Overall, the results presented herein contribute to the growing literature on a microbial dysbiosis and the impact of specific microbial taxa on symptoms in children with ASD. Importantly, this research offers new insight into the effect of diet on the microbiota composition, microbial metabolism and the temporal variability in children with ASD. Future studies are warranted to analyze whether dietary intake could potentially be a modifiable moderator of the microbiota-symptoms connections in ASD.LimitedAuthor requested closed access (OA after 2yrs) in Vireo ETD syste