scholarly journals Alterations in Gut Glutamate Metabolism Associated with Changes in Gut Microbiota Composition in Children with Autism Spectrum Disorder

mSystems ◽  
2019 ◽  
Vol 4 (1) ◽  
pp. e00321-18 ◽  
Author(s):  
Mingbang Wang ◽  
Jing Wan ◽  
Han Rong ◽  
Fusheng He ◽  
Hui Wang ◽  
...  

ABSTRACT Changes in the gut microenvironment may influence the pathogenesis of autism spectrum disorders (ASD). Here, we investigated the composition of the gut microbiota and metabolites in children with ASD. Ninety-two children with ASD and 42 age-matched children exhibiting typical development (TD) were enrolled in the two-stage study. In the discovery stage, shotgun metagenomic sequencing and liquid chromatography-mass spectrometry (LC-MS) were performed simultaneously on fecal samples obtained from 43 children in the ASD group and 31 children in the TD group. Systematic bioinformatic analyses were performed to identify gut metabolites associated with altered gut microbiota composition. At the validation stage, differential metabolites were tested using LC-MS with an additional 49 and 11 children in the ASD and TD groups, respectively. Altered glutamate metabolites were found in the ASD group, along with a decline in 2-keto-glutaramic acid and an abundance of microbiota associated with glutamate metabolism. These changes in glutamate metabolism were correlated with lower levels of the highly abundant bacteria Bacteroides vulgatus and higher levels of the potentially harmful Eggerthella lenta and Clostridium botulinum. Lower gut cortisol levels have also been identified in the ASD group and associated with changes in gut microbiota glutamate metabolism. Finally, gut 2-keto-glutaramic acid was validated as a potential biomarker for ASD. The significant changes in the gut microenvironment in children with ASD may provide new insight into the cause of ASD and aid in the search for diagnostic and therapeutic approaches. IMPORTANCE Multiple lines of evidence suggest that the gut microbiota may play an important role in the pathogenesis of ASD, but the specific mechanism is still unclear. Through a comprehensive gut metagenomic and metabolome study of children with ASD, alterations in gut metabolite composition were found in children with ASD, and these alterations were linked to changes in gut microbiota composition. This may give us a deeper understanding of the role of gut microbiota in the pathogenesis of ASD.

2018 ◽  
Vol 48 (6) ◽  
pp. 962-972 ◽  
Author(s):  
Rio Jati Kusuma ◽  
Aviria Ermamilia

Purpose Iron deficiency anemia (IDA) is one of the most major micronutrient deficiencies worldwide. Food fortification is one strategy for reducing IDA in the population despite concern regarding the gut pathogenic bacteria overgrowth. The purpose of this study was to evaluate the effect of iron encapsulation in banana peel matrix on iron status and gut microbiota composition in iron deficiency anemia. Design/methodology/approach Anemia was induced in 35 male Sprague Dawley rats of age two weeks by the administration of iron-free diet for two weeks. Rats then randomly divided into control, iron-fortified tempeh (temFe) dose 10 and 20 ppm, iron matrix-fortified tempeh dose 10 and 20 ppm and iron matrix fortified tempeh dose 10 and 20 ppm with probiotic mixture. Blood was drawn at Weeks 2 and 6 for hemoglobin and serum iron analysis. Rats were sacrificed at the end of Week 6, and cecal contents were collected for Lactobacillus, Bifidobacteria and Enterobactericeae analysis. Findings Hemoglobin and serum iron were significantly increased (p < 0.05) in all iron-fortified group with the highest value found in iron matrix dose 20 ppm (10.71 ± 0.15 g/dl and 335.83 ± 2.17 µg/dl, respectively). The cecal Lactobacillus and Bifidobacteria did not differ significantly between groups. Cecal Enterobactericeae was significantly different (p < 0.05) among groups with the lowest level in the temFe-20 (2.65 ± 0.78 log CFU) group. Research limitations/implications The use of commercial inoculum instead of pure Rhizopus oligosporus mold for developing the fortified tempeh may impact the effect of product on cecal gut microbiota composition, as different molds and lactic acid bacteria can grow in tempeh when using commercial inoculum. Social implications In Indonesia, iron fortification is conducted primarily in noodles and flour that limits the impact of iron fortification for reducing IDA in population. Iron fortification in food that was daily consumed by people, that is, tempeh, is potential strategy in reducing IDA in population. Originality/value Tempeh fortification using encapsulated iron improved iron status and gut microbiota composition in iron deficiency anemia.


2021 ◽  
Author(s):  
Peifeng Xie ◽  
Chengjun Hu ◽  
Qinghua He ◽  
Qian Zhu ◽  
Xiangfeng Kong

Abstract Background Gut microbiota and their metabolites were associated with obesity. Our previous study showed that maternal body fat percentage increased from days 45 to 110 of gestation in a Huanjiang mini-pig model. Thus, 16S rRNA sequencing and metabonomic techniques were used to investigate the changes of maternal gut microbiota composition and microbial metabolite profile from days 45 to 110 of gestation. Results The abundances of Clostridium_sensu_stricto_1, Romboutsia, Turicibacter, and Streptococcus in jejunum contents were higher in day 110 than those in day 45 or 75 of gestation. In ileum, the abundance of Streptococcus was the highest (P < 0.05) at day 110 of gestation, as well as the metabolism function of jejunal and ileal microbiota. The ileal butyrate and acetate concentrations were the highest at day 45 and day 110 of gestation, respectively. In colon, the concentrations of cadaverine and spermine were the highest (P < 0.05) at days 45 and 110 of gestation, respectively. Metabonomic analysis demonstrated that metabolic pathways including glutamine and glutamate metabolism, phenylalanine, tyrosine and tryptophan biosynthesis, and alanine, aspartate, and glutamate metabolism changed during gestation. Conclusions Microbiota composition and metabolites changed dramatically from the early to the late pregnancy, which might be associated with the maternal fat accumulation.


2020 ◽  
Vol 79 (OCE2) ◽  
Author(s):  
Anna M. Malinowska ◽  
Marcin Schmidt ◽  
Agata Chmurzynska

AbstractHuman gut microbiota may affect metabolism and health by synthesizing metabolites and processing of food components. Those processes are specific to genus and species (or even strain), and dietary intake and metabolic state (such as obesity) can affect the composition of gut microbiota. The aim of the study was to assess the effect of dietary patterns and intake of several groups of food products and macronutrients, as well as the impact of anthropometric parameters on gut microbiota composition.The study group consisted of 200 men and women between 31 and 50 years of age. The diet was assessed using three-day dietary records and the dietary pattern was determined with the use of the original score method and two dietary indices, namely the Diet Quality Index – International (DQI-I) and the Healthy Eating Index (HEI). Bacterial DNA was isolated from the feces of the participants and microbiota composition was determined using metagenomic sequencing of the V3–V4 region of the 16S rRNA gene.Dietary indices and intake of energy from macronutrients did not correlate with the Firmicutes to Bacteroidetes phylum ratio. However people with greater abundance of the Firmicutes phylum compared to Bacteroidetes consumed higher amounts of fermented milk beverages, hard cheese, and salt (78%, 48%, 14% higher intake respectively; p < 0.05). A higher diet quality as measured by the diet indices was positively correlated with the relative abundance of the Firmicutes phylum, Bacilli, Clostridia class, Lachnospira, Faecalibacterium, Coprococcus, and Prevotella genus and negatively correlated with the relative abundance of the Bacteroidetes phylum, Bacteroidia class, and Bacteroides genus. Higher dietary fiber intake positively correlated with the relative abundance of the Coprococcus, Lachnospira, and Roseburia genera, whereas energy intake from simple carbohydrates was positively correlated with the relative abundance of the Tenericutes phylum and the Mollicutes class. Energy intake from alcohol correlated positively with the relative abundance of Bacteroidetes phylum and Bacteroides class and correlated negatively with Firmicutes phylum and Clostridia class. Lower waist-to-hip-ratio, body mass index, and fat mass led to higher abundance of the Fecalibacterium genus.Both diet and anthropometric parameters are associated with gut microbiota composition. Associations between diet and the relative abundance of microbiota are nutrient-specific.


Author(s):  
Stina Ramne ◽  
Louise Brunkwall ◽  
Ulrika Ericson ◽  
Nicola Gray ◽  
Gunter G. C. Kuhnle ◽  
...  

Abstract Purpose It has been suggested that a high intake of sugar or sweeteners may result in an unfavorable microbiota composition; however, evidence is lacking. Hence, in this exploratory epidemiological study, we aim to examine if intake of added sugar, sugar-sweetened beverages (SSBs) or artificially sweetened beverages (ASBs) associate with the gut microbiota composition. Methods Participants (18–70 years) in the Malmö Offspring Study have provided blood, urine, and fecal samples and completed both web-based 4 day food records and short food frequency questionnaires. The gut microbiota was assessed by 16S rRNA sequencing, processed in QIIME and matched to Greengenes (v.13.8), giving 64 included genera after filtering. Intake of added sugar (n = 1371) (also supported by the overnight urinary sugar biomarker in a subgroup n = 577), SSBs (n = 1086) and ASBs (n = 1085) were examined as exposures in negative binomial regressions. Results Various genera nominally associated with intake of added sugar, SSBs, and ASBs. Only the negative association between SSB intake and Lachnobacterium remained significant after multiple testing correction. A positive association between SSB intake and the Firmicutes:Bacteroidetes ratio was also observed. Conclusion In this wide population, the cross-sectional associations between added sugar and sweet beverage intake and the gut microbiota are modest, but the results suggest that SSB intake is associated negatively with the genus Lachnobacterium and positively with the Firmicutes:Bacteroidetes ratio. Larger studies, preferably using metagenomic sequencing, are needed to further evaluate if a link exists between intake of sugars and sweeteners and the human gut microbiota.


2017 ◽  
Vol 7 (1) ◽  
Author(s):  
Lorena Coretti ◽  
Claudia Cristiano ◽  
Ermanno Florio ◽  
Giovanni Scala ◽  
Adriano Lama ◽  
...  

2021 ◽  
Vol 22 (18) ◽  
pp. 10028
Author(s):  
Julia Doroszkiewicz ◽  
Magdalena Groblewska ◽  
Barbara Mroczko

The gut microbiome has attracted increasing attention from researchers in recent years. The microbiota can have a specific and complex cross-talk with the host, particularly with the central nervous system (CNS), creating the so-called “gut–brain axis”. Communication between the gut, intestinal microbiota, and the brain involves the secretion of various metabolites such as short-chain fatty acids (SCFAs), structural components of bacteria, and signaling molecules. Moreover, an imbalance in the gut microbiota composition modulates the immune system and function of tissue barriers such as the blood–brain barrier (BBB). Therefore, the aim of this literature review is to describe how the gut–brain interplay may contribute to the development of various neurological disorders, combining the fields of gastroenterology and neuroscience. We present recent findings concerning the effect of the altered microbiota on neurodegeneration and neuroinflammation, including Alzheimer’s and Parkinson’s diseases, as well as multiple sclerosis. Moreover, the impact of the pathological shift in the microbiome on selected neuropsychological disorders, i.e., major depressive disorders (MDD) and autism spectrum disorder (ASD), is also discussed. Future research on the effect of balanced gut microbiota composition on the gut–brain axis would help to identify new potential opportunities for therapeutic interventions in the presented diseases.


mBio ◽  
2014 ◽  
Vol 5 (5) ◽  
Author(s):  
Johan Dicksved ◽  
Patrik Ellström ◽  
Lars Engstrand ◽  
Hilpi Rautelin

ABSTRACTThe gut microbiota is essential for human health, but very little is known about how the composition of this ecosystem can influence and respond to bacterial infections. Here we address this by prospectively studying the gut microbiota composition before, during, and after naturalCampylobacterinfection in exposed poultry abattoir workers. The gut microbiota composition was analyzed with 16S amplicon sequencing of fecal samples from poultry abattoir workers during the peak season ofCampylobacterinfection in Sweden. The gut microbiota compositions were compared between individuals who became culture positive forCampylobacterand those who remained negative. Individuals who becameCampylobacterpositive had a significantly higher abundance ofBacteroides(P= 0.007) andEscherichia(P= 0.002) species than those who remained culture negative. Furthermore, this group had a significantly higher abundance ofPhascolarctobacterium(P= 0.017) andStreptococcus(P= 0.034) sequences than theCampylobacter-negative group, which had an overrepresentation ofClostridiales(P= 0.017), unclassifiedLachnospiraceae(P= 0.008), andAnaerovorax(P= 0.015) sequences. Intraindividual comparisons of the fecal microbiota compositions yielded small differences over time inCampylobacter-negative participants, but significant long-term changes were found in theCampylobacter-positive group (P< 0.005). The results suggest that the abundance of specific genera in the microbiota reduces resistance toCampylobactercolonization in humans and thatCampylobacterinfection can have long-term effects on the composition of the human fecal microbiota.IMPORTANCEStudies using mouse models have made important contributions to our understanding of the role of the gut microbiota in resistance to bacterial enteropathogen colonization. The relative abundances ofEscherichia coliandBacteroidesspecies have been pointed out as important determinants of susceptibility to Gram-negative pathogens in general andCampylobacterinfection in particular. In this study, we assessed the role of the human gut microbiota in resistance toCampylobactercolonization by studying abattoir workers that are heavily exposed to these bacteria. Individuals with a certain composition of the gut microbiota became culture positive forCampylobacter. As their microbiotas were characterized by high abundances ofBacteroidesspp. andE. coli, well in line with the findings with mouse models, these bacterial species likely play an important role in colonization resistance also in humans.


2021 ◽  
Author(s):  
Shuangshuang Wang ◽  
Feng Song ◽  
Haoyu Gu ◽  
Zhilong Shu ◽  
Xiaowen Wei ◽  
...  

Abstract Background: Human gut microbiota is individually unique that hints the microbiota in fecal traces left in the crime scene could act as a potential biomarker for forensic personal identification. Next-generation DNA sequencing and bioinformatic analysis of fecal samples are revolutionizing our insights into gut microbial communities. While the formation of the gut microbiota is known to be multifactorial, it is unclear whether these characteristics can be applied to forensic applications. Therefore, the gut microbiota of healthy adults with different traits in Chengdu was investigated in this study.Results: Based on the STAMP analysis of each study group, the difference in gut microbiota composition in male and female subjects was observed. The male group was characterized by taxa in the phylum Proteobacteria, while the female group was described by Synergistetes phylum. The gut bacterial community assembly mechanism was mainly affected by the deterministic process. In addition, gut microbiota composition showed meaningful discrimination in each of the BMI groups. At the phylum level, in male subjects, increased representative phyla were Patescibacteria (p<0.05) in the underweight group and Bacteroidetes (p<0.05) in the normal-weight group, while in the female group, the significantly different phyla were Bacteroidetes, Firmicutes, and Actinobacteria. At the genus level, 44 unique genera were found to be significantly distinct across BMI study groups. By Fisher’s Linear Discriminant Analysis based on 38 of 44 unique genera, 94.4% of original BMI grouped subjects were correctly classified.Conclusion: In conclusion, subjects with different individual characters have specific gut microbiota, and can be discriminated by bioinformatics methods, suggesting it is promising to apply gut microbiota to forensic personal identification.


mSphere ◽  
2018 ◽  
Vol 3 (5) ◽  
Author(s):  
Tamotsu Kato ◽  
Kyoko Yamazaki ◽  
Mayuka Nakajima ◽  
Yasuhiro Date ◽  
Jun Kikuchi ◽  
...  

ABSTRACTPeriodontal disease induced by periodontopathic bacteria likePorphyromonas gingivalisis demonstrated to increase the risk of metabolic, inflammatory, and autoimmune disorders. Although precise mechanisms for this connection have not been elucidated, we have proposed mechanisms by which orally administered periodontopathic bacteria might induce changes in gut microbiota composition, barrier function, and immune system, resulting in an increased risk of diseases characterized by low-grade systemic inflammation. Accumulating evidence suggests a profound effect of altered gut metabolite profiles on overall host health. Therefore, it is possible thatP. gingivaliscan affect these metabolites. To test this, C57BL/6 mice were administered withP. gingivalisW83 orally twice a week for 5 weeks and compared with sham-inoculated mice. The gut microbial communities were analyzed by pyrosequencing the 16S rRNA genes. Inferred metagenomic analysis was used to determine the relative abundance of KEGG pathways encoded in the gut microbiota. Serum metabolites were analyzed using nuclear magnetic resonance (NMR)-based metabolomics coupled with multivariate statistical analyses. Oral administration ofP. gingivalisinduced a change in gut microbiota composition. The distributions of metabolic pathways differed between the two groups, including those related to amino acid metabolism and, in particular, the genes for phenylalanine, tyrosine, and tryptophan biosynthesis. Also, alanine, glutamine, histidine, tyrosine, and phenylalanine were significantly increased in the serum ofP. gingivalis-administered mice. In addition to altering immune modulation and gut barrier function, oral administration ofP. gingivalisaffects the host’s metabolic profile. This supports our hypothesis regarding a gut-mediated systemic pathology resulting from periodontal disease.IMPORTANCEIncreasing evidence suggest that alterations of the gut microbiome underlie metabolic disease pathology by modulating gut metabolite profiles. We have shown that orally administeredPorphyromonas gingivalis, a representative periodontopathic bacterium, alters the gut microbiome; that may be a novel mechanism by which periodontitis increases the risk of various diseases. Given the association between periodontal disease and metabolic diseases, it is possible thatP. gingivaliscan affect the metabolites. Metabolite profiling analysis demonstrated that several amino acids related to a risk of developing diabetes and obesity were elevated inP. gingivalis-administered mice. Our results revealed that the increased risk of various diseases byP. gingivalismight be mediated at least in part by alteration of metabolic profiles. The findings should add new insights into potential links between periodontal disease and systemic disease for investigators in periodontal disease and also for investigators in the field of other diseases, such as metabolic diseases.


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