Autism spectrum disorder (ASD) is a neurodevelopmental disorder that is characterized by impairments in social interactions and communication, restricted interests and repetitive behaviors. Several ...studies report a high prevalence of gastrointestinal (GI) symptoms in autistic individuals. Cumulative evidence reveals that the gut microbiota and its metabolites (especially short-chain fatty acids, SCFAs) play an important role in GI disorders and the pathogenesis of ASD. However, the composition of the gut microbiota and its association with fecal SCFAs and GI symptoms of autistic children remain largely unknown. In the present study, we sequenced the bacterial 16S rRNA gene, detected fecal SCFAs, assessed GI symptoms and analyzed the relationship between the gut microbiome and fecal SCFAs in autistic and neurotypical individuals. The results showed that the compositions of the gut microbiota and SCFAs were altered in ASD individuals. We found lower levels of fecal acetic acid and butyrate and a higher level of fecal valeric acid in ASD subjects. We identified decreased abundances of key butyrate-producing taxa (Ruminococcaceae, Eubacterium, Lachnospiraceae and Erysipelotrichaceae) and an increased abundance of valeric acid associated bacteria (Acidobacteria) among autistic individuals. Constipation was the only GI disorder in ASD children in the present study. We also found enriched Fusobacterium, Barnesiella, Coprobacter and valeric acid-associated bacteria (Actinomycetaceae) and reduced butyrate-producing taxa in constipated autistic subjects. It is suggested that the gut microbiota contributes to fecal SCFAs and constipation in autism. Modulating the gut microbiota, especially butyrate-producing bacteria, could be a promising strategy in the search for alternatives for the treatment of autism spectrum disorder.
Many studies have reported abnormal gut microbiota in individuals with Autism Spectrum Disorders (ASD), suggesting a link between gut microbiome and autism-like behaviors. Modifying the gut ...microbiome is a potential route to improve gastrointestinal (GI) and behavioral symptoms in children with ASD, and fecal microbiota transplant could transform the dysbiotic gut microbiome toward a healthy one by delivering a large number of commensal microbes from a healthy donor. We previously performed an open-label trial of Microbiota Transfer Therapy (MTT) that combined antibiotics, a bowel cleanse, a stomach-acid suppressant, and fecal microbiota transplant, and observed significant improvements in GI symptoms, autism-related symptoms, and gut microbiota. Here, we report on a follow-up with the same 18 participants two years after treatment was completed. Notably, most improvements in GI symptoms were maintained, and autism-related symptoms improved even more after the end of treatment. Important changes in gut microbiota at the end of treatment remained at follow-up, including significant increases in bacterial diversity and relative abundances of Bifidobacteria and Prevotella. Our observations demonstrate the long-term safety and efficacy of MTT as a potential therapy to treat children with ASD who have GI problems, and warrant a double-blind, placebo-controlled trial in the future.
Characterizing the microbial communities inhabiting specimens is one of the primary objectives of microbiome studies. A short-read sequencing platform for reading partial regions of the 16S rRNA gene ...is most commonly used by reducing the cost burden of next-generation sequencing (NGS), but misclassification at the species level due to its length being too short to consider sequence similarity remains a challenge. Loop Genomics recently proposed a new 16S full-length-based synthetic long-read sequencing technology (sFL16S). We compared a 16S full-length-based synthetic long-read (sFL16S) and V3-V4 short-read (V3V4) methods using 24 human GUT microbiota samples. Our comparison analyses of sFL16S and V3V4 sequencing data showed that they were highly similar at all classification resolutions except the species level. At the species level, we confirmed that sFL16S showed better resolutions than V3V4 in analyses of alpha-diversity, relative abundance frequency and identification accuracy. Furthermore, we demonstrated that sFL16S could overcome the microbial misidentification caused by different sequence similarity in each 16S variable region through comparison the identification accuracy of Bifidobacterium, Bacteroides, and Alistipes strains classified from both methods. Therefore, this study suggests that the new sFL16S method is a suitable tool to overcome the weakness of the V3V4 method.
Systematic characterization of the cancer microbiome provides the opportunity to develop techniques that exploit non-human, microorganism-derived molecules in the diagnosis of a major human disease. ...Following recent demonstrations that some types of cancer show substantial microbial contributions
, we re-examined whole-genome and whole-transcriptome sequencing studies in The Cancer Genome Atlas
(TCGA) of 33 types of cancer from treatment-naive patients (a total of 18,116 samples) for microbial reads, and found unique microbial signatures in tissue and blood within and between most major types of cancer. These TCGA blood signatures remained predictive when applied to patients with stage Ia-IIc cancer and cancers lacking any genomic alterations currently measured on two commercial-grade cell-free tumour DNA platforms, despite the use of very stringent decontamination analyses that discarded up to 92.3% of total sequence data. In addition, we could discriminate among samples from healthy, cancer-free individuals (n = 69) and those from patients with multiple types of cancer (prostate, lung, and melanoma; 100 samples in total) solely using plasma-derived, cell-free microbial nucleic acids. This potential microbiome-based oncology diagnostic tool warrants further exploration.
The genome sequences of many species of the human gut microbiome remain unknown, largely owing to challenges in cultivating microorganisms under laboratory conditions. Here we address this problem by ...reconstructing 60,664 draft prokaryotic genomes from 3,810 faecal metagenomes, from geographically and phenotypically diverse humans. These genomes provide reference points for 2,058 newly identified species-level operational taxonomic units (OTUs), which represents a 50% increase over the previously known phylogenetic diversity of sequenced gut bacteria. On average, the newly identified OTUs comprise 33% of richness and 28% of species abundance per individual, and are enriched in humans from rural populations. A meta-analysis of clinical gut-microbiome studies pinpointed numerous disease associations for the newly identified OTUs, which have the potential to improve predictive models. Finally, our analysis revealed that uncultured gut species have undergone genome reduction that has resulted in the loss of certain biosynthetic pathways, which may offer clues for improving cultivation strategies in the future.
Social relationships shape human health and mortality via behavioral, psychosocial, and physiological mechanisms, including inflammatory and immune responses. Though not tested in human studies, ...recent primate studies indicate that the gut microbiome may also be a biological mechanism linking relationships to health. Integrating microbiota data into the 60-year-old Wisconsin Longitudinal Study, we found that socialness with family and friends is associated with differences in the human fecal microbiota. Analysis of spouse (N = 94) and sibling pairs (N = 83) further revealed that spouses have more similar microbiota and more bacterial taxa in common than siblings, with no observed differences between sibling and unrelated pairs. These differences held even after accounting for dietary factors. The differences between unrelated individuals and married couples was driven entirely by couples who reported close relationships; there were no differences in similarity between couples reporting somewhat close relationships and unrelated individuals. Moreover, married individuals harbor microbial communities of greater diversity and richness relative to those living alone, with the greatest diversity among couples reporting close relationships, which is notable given decades of research documenting the health benefits of marriage. These results suggest that human interactions, especially sustained, close marital relationships, influence the gut microbiota.
With the rising plastic pollution in the oceans, research on the plastispherethe microorganisms interacting with marine plastic debrishas emerged. Microbial communities colonizing plastic have been ...characterized from several ocean regions and they are distinct from the communities of the surrounding waters, and a few plastic-degrading microorganisms have been isolated from other environments. Therefore, we propose that marine microorganisms have adapted to plastic as a surface for colonization and potentially degradation. When comparing the taxonomic patterns of plastic-associated, marine bacteria, recurring groups and families such as the families Erythrobacteraceae and Rhodobacteraceae (Alphaproteobacteria), Flavobacteriaceae (Bacteriodetes), and the phylum of cyanobacteria (such as the Phormidium genus) can be identified. Thereby, we provide a perspective on which bacterial candidates could play a role in the colonization and possible degradation of plastic in the oceans due to their occurrence on marine plastic debris. We emphasize the need for extended and reproducible collection of data to assess the existence of a core microbiome or core functionalities of the plastisphere and confirm the capability of these bacterial candidates for biodegradation of plastic. Furthermore, we suggest the next steps in research to elucidate the level of natural bioremediation and the exploitation of bacterial degradative mechanisms of plastic.
Soils harbour some of the most diverse microbiomes on Earth and are essential for both nutrient cycling and carbon storage. To understand soil functioning, it is necessary to model the global ...distribution patterns and functional gene repertoires of soil microorganisms, as well as the biotic and environmental associations between the diversity and structure of both bacterial and fungal soil communities
. Here we show, by leveraging metagenomics and metabarcoding of global topsoil samples (189 sites, 7,560 subsamples), that bacterial, but not fungal, genetic diversity is highest in temperate habitats and that microbial gene composition varies more strongly with environmental variables than with geographic distance. We demonstrate that fungi and bacteria show global niche differentiation that is associated with contrasting diversity responses to precipitation and soil pH. Furthermore, we provide evidence for strong bacterial-fungal antagonism, inferred from antibiotic-resistance genes, in topsoil and ocean habitats, indicating the substantial role of biotic interactions in shaping microbial communities. Our results suggest that both competition and environmental filtering affect the abundance, composition and encoded gene functions of bacterial and fungal communities, indicating that the relative contributions of these microorganisms to global nutrient cycling varies spatially.
Individuals vary widely in their responses to medicinal drugs, which can be dangerous and expensive owing to treatment delays and adverse effects. Although increasing evidence implicates the gut ...microbiome in this variability, the molecular mechanisms involved remain largely unknown. Here we show, by measuring the ability of 76 human gut bacteria from diverse clades to metabolize 271 orally administered drugs, that many drugs are chemically modified by microorganisms. We combined high-throughput genetic analyses with mass spectrometry to systematically identify microbial gene products that metabolize drugs. These microbiome-encoded enzymes can directly and substantially affect intestinal and systemic drug metabolism in mice, and can explain the drug-metabolizing activities of human gut bacteria and communities on the basis of their genomic contents. These causal links between the gene content and metabolic activities of the microbiota connect interpersonal variability in microbiomes to interpersonal differences in drug metabolism, which has implications for medical therapy and drug development across multiple disease indications.
Within the past 5 years, tremendous advances have been made to maximize the performance of microbial fuel cells (MFCs) for both “clean” bioenergy production and bioremediation. Most research efforts ...have focused on parameters including (i) optimizing reactor configuration, (ii) electrode construction, (iii) addition of redox-active, electron donating mediators, (iv) biofilm acclimation and feed nutrient adjustment, as well as (v) other parameters that contribute to enhanced MFC performance. To date, tremendous advances have been made, but further improvements are needed for MFCs to be economically practical. In this review, the diversity of electrogenic microorganisms and microbial community changes in mixed cultures are discussed. More importantly, different approaches including chemical/genetic modifications and gene regulation of exoelectrogens, synthetic biology approaches and bacterial community cooperation are reviewed. Advances in recent years in metagenomics and microbiomes have allowed researchers to improve bacterial electrogenicity of robust biofilms in MFCs using novel, unconventional approaches. Taken together, this review provides some important and timely information to researchers who are examining additional means to enhance power production of MFCs.
•Numerous electrogenic microorganisms for microbial fuel cells (MFCs) are reviewed.•The impact of microbiota changes in biofilms on electrogenicity is discussed.•Chemical and genetic techniques that enhance biofilm electrogenicity are reviewed.•A forward-looking synthetic biology approach to enhance power output is presented.
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