Deviated and early unsustainable stunted development of gut microbiota in children with autism spectrum disorder.

OBJECTIVE: Recent studies have provided insights into the gut microbiota in autism spectrum disorder (ASD); however, these studies were restricted owing to limited sampling at the unitary stage of childhood. Herein, we aimed to reveal developmental characteristics of gut microbiota in a large cohort of subjects with ASD combined with interindividual factors impacting gut microbiota. DESIGN: A large cohort of 773 subjects with ASD (aged 16 months to 19 years), 429 neurotypical (NT) development subjects (aged 11 months to 15 years) were emolyed to determine the dynamics change of gut microbiota across different ages using 16S rRNA sequencing. RESULT: In subjects with ASD, we observed a distinct but progressive deviation in the development of gut microbiota characterised by persistently decreased alpha diversity, early unsustainable immature microbiota, altered aboudance of 20 operational taxonomic units (OTUs), decreased taxon detection rate and 325 deregulated microbial metabolic functions with age-dependent patterns. We further revealed microbial relationships that have changed extensively in ASD before 3 years of age, which were associated with the severity of behaviour, sleep and GI symptoms in the ASD group. This analysis demonstrated that a signature of the combination of 2 OTUs, Veillonella and Enterobacteriaceae, and 17 microbial metabolic functions efficiently discriminated ASD from NT subjects in both the discovery (area under the curve (AUC)=0.86), and validation 1 (AUC=0.78), 2 (AUC=0.82) and 3 (AUC=0.67) sets. CONCLUSION: Our large cohort combined with clinical symptom analysis highlights the key regulator of gut microbiota in the pathogenesis of ASD and emphasises the importance of monitoring and targeting the gut microbiome in future clinical applications of ASD.

A multiple-dimension model for microbiota of patients with colorectal cancer from normal participants and other intestinal disorders.

Gut microbiota is a primary driver of inflammation in the colon and is linked to early colorectal cancer (CRC) development. Thus, a novel and noninvasive microbiome-based model could promote screening in patients at average risk for CRC. Nevertheless, the relevance and effectiveness of microbial biomarkers for noninvasive CRC screening remains unclear, and researchers lack the data to distinguish CRC-related gut microbiome biomarkers from those of other common gastrointestinal (GI) diseases. Microbiome-based classification distinguishes patients with CRC from normal participants and excludes other CRC-relevant diseases (e.g., GI bleed, adenoma, bowel diseases, and postoperative). The area under the receiver operator characteristic curve (AUC) was 92.2%. Known associations with oral pathogenic features, benefits-generated features, and functional features of CRC were confirmed using the model. Our optimised prediction model was established using large-scale experimental population-based data and other sequence-based faecal microbial community data. This model can be used to identify the high-risk groups and has the potential to become a novel screening method for CRC biomarkers because of its low false-positive rate (FPR) and good stability. KEY POINTS: • A total of 5744 CRC and non-CRC large-scale faecal samples were sequenced, and a model was constructed for CRC discrimination on the basis of the relative abundance of taxonomic and functional features. • This model could identify high-risk groups and become a novel screening method for CRC biomarkers because of its low FPR and good stability. • The association relationship of oral pathogenic features, benefits-generated features, and functional features in CRC was confirmed by the study.

Characteristics of gastric cancer gut microbiome according to tumor stage and age segmentation.

With the development of 16S rRNA technology, gut microbiome evaluation has been performed in many diseases, including gastrointestinal tumors. Among these cancers, gastric cancer (GC) exhibits high morbidity and mortality and has been extensively studied in its pathogenesis and diagnosis techniques. The current researches have proved that the gut microbiome may have the potential to distinguish GC patients from healthy patients. However, the change of the gut microbiome according to tumor node metastasis classification (TNM) has not been clarified. Besides, the characteristics of gut microbiome in GC patients and their ages of onset are also ambiguous. To address the above shortcomings, we investigated 226 fecal samples and divided them according to their tumor stage and onset age. The findings revealed that surgery and tumor stage can change the characteristic of GC patients' gut microbiota. In specific, the effect of surgery on early gastric cancer (EGC) was greater than that on advanced gastric cancer (AGC), and the comparison of postoperative microflora with healthy people indicated that EGC has more differential bacteria than AGC. Besides, we found that Collinsella, Blautia, Anaerostipes, Dorea, and Lachnospiraceae_ND3007_group expressed differently between EGC and AGC. More importantly, it is the first time revealed that the composition of gut microbiota in GC is different between different onset ages. KEY POINTS: •Gut microbiota of gastric cancer (GC) patients are either highly associated with TNM stage and surgery or not. It shows surgery has more significant changes in early gastric cancer (EGC) than advanced gastric cancer (AGC). •There existed specific gut microbiota between EGC and AGC which may have potential to distinguish the early or advanced GC. •Onset age of GC may influence the gut microbiota: the composition of gut microbiota of early-onset gastric cancer (EOGC) and late-onset gastric cancer (LOGC) is significantly different.

Gut microbiome analysis as a predictive marker for the gastric cancer patients.

Gut microbiota have been implicated in the development of cancer. Colorectal and gastric cancers, the major gastrointestinal tract cancers, are closely connected with the gut microbiome. Nevertheless, the characteristics of gut microbiota composition that correlate with gastric cancer are unclear. In this study, we investigated gut microbiota alterations during the progression of gastric cancer to identify the most relevant taxa associated with gastric cancer and evaluated the potential of the microbiome as an indicator for the diagnosis of gastric cancer. Compared with the healthy group, gut microbiota composition and diversity shifted in patients with gastric cancer. Different bacteria were used to design a random forest model, which provided an area under the curve value of 0.91. Verification samples achieved a true positive rate of 0.83 in gastric cancer. Principal component analysis showed that gastritis shares some microbiome characteristics of gastric cancer. Chemotherapy reduced the elevated bacteria levels in gastric cancer by more than half. More importantly, we found that the genera Lactobacillus and Megasphaera were associated with gastric cancer.Key Points• Gut microbiota has high sensitivity and specificity in distinguishing patients with gastric cancer from healthy individuals, indicating that gut microbiota is a potential noninvasive tool for the diagnosis of gastric cancer.• Gastritis shares some microbiota features with gastric cancer, and chemotherapy reduces the microbial abundance and diversity in gastric cancer patients.• Two bacterial taxa, namely, Lactobacillus and Megasphaera, are predictive markers for gastric cancer.

Genomic adaptation to drought in wild barley is driven by edaphic natural selection at the Tabigha Evolution Slope.

Ecological divergence at a microsite suggests adaptive evolution, and this study examined two abutting wild barley populations, each 100 m across, differentially adapted to drought tolerance on two contrasting soil types, Terra Rossa and basalt at the Tabigha Evolution Slope, Israel. We resequenced the genomes of seven and six wild barley genotypes inhabiting the Terra Rossa and basalt soils, respectively, and identified a total of 69,192,653 single-nucleotide variants (SNVs) and insertions/deletions in comparison with a reference barley genome. Comparative genomic analysis between these abutting wild barley populations involved 19,615,087 high-quality SNVs. The results revealed dramatically different selection sweep regions relevant to drought tolerance driven by edaphic natural selection within 2,577 selected genes in these regions, including key drought-responsive genes associated with ABA synthesis and degradation (such as Cytochrome P450 protein) and ABA receptor complex (such as PYL2, SNF1-related kinase). The genetic diversity of the wild barley population inhabiting Terra Rossa soil is much higher than that from the basalt soil. Additionally, we identified different sets of genes for drought adaptation in the wild barley populations from Terra Rossa soil and from wild barley populations from Evolution Canyon I at Mount Carmel. These genes are associated with abscisic acid signaling, signaling and metabolism of reactive oxygen species, detoxification and antioxidative systems, rapid osmotic adjustment, and deep root morphology. The unique mechanisms for drought adaptation of the wild barley from the Tabigha Evolution Slope may be useful for crop improvement, particularly for breeding of barley cultivars with high drought tolerance.

Assembly and analysis of a qingke reference genome demonstrate its close genetic relation to modern cultivated barley.

Qingke, the local name of hulless barley in the Tibetan Plateau, is a staple food for Tibetans. The availability of its reference genome sequences could be useful for studies on breeding and molecular evolution. Taking advantage of the third-generation sequencer (PacBio), we de novo assembled a 4.84-Gb genome sequence of qingke, cv. Zangqing320 and anchored a 4.59-Gb sequence to seven chromosomes. Of the 46,787 annotated 'high-confidence' genes, 31 564 were validated by RNA-sequencing data of 39 wild and cultivated barley genotypes with wide genetic diversity, and the results were also confirmed by nonredundant protein database from NCBI. As some gaps in the reference genome of Morex were covered in the reference genome of Zangqing320 by PacBio reads, we believe that the Zangqing320 genome provides the useful supplements for the Morex genome. Using the qingke genome as a reference, we conducted a genome comparison, revealing a close genetic relationship between a hulled barley (cv. Morex) and a hulless barley (cv. Zangqing320), which is strongly supported by the low-diversity regions in the two genomes. Considering the origin of Morex from its breeding pedigree, we then demonstrated a close genomic relationship between modern cultivated barley and qingke. Given this genomic relationship and the large genetic diversity between qingke and modern cultivated barley, we propose that qingke could provide elite genes for barley improvement.

Transcriptome profiling reveals mosaic genomic origins of modern cultivated barley.

The domestication of cultivated barley has been used as a model system for studying the origins and early spread of agrarian culture. Our previous results indicated that the Tibetan Plateau and its vicinity is one of the centers of domestication of cultivated barley. Here we reveal multiple origins of domesticated barley using transcriptome profiling of cultivated and wild-barley genotypes. Approximately 48-Gb of clean transcript sequences in 12 Hordeum spontaneum and 9 Hordeum vulgare accessions were generated. We reported 12,530 de novo assembled transcripts in all of the 21 samples. Population structure analysis showed that Tibetan hulless barley (qingke) might have existed in the early stage of domestication. Based on the large number of unique genomic regions showing the similarity between cultivated and wild-barley groups, we propose that the genomic origin of modern cultivated barley is derived from wild-barley genotypes in the Fertile Crescent (mainly in chromosomes 1H, 2H, and 3H) and Tibet (mainly in chromosomes 4H, 5H, 6H, and 7H). This study indicates that the domestication of barley may have occurred over time in geographically distinct regions.

Phosphorus and magnesium interactively modulate the elongation and directional growth of primary roots in Arabidopsis thaliana (L.) Heynh.

A balanced supply of essential nutrients is an important factor influencing root architecture in many plants, yet data related to the interactive effects of two nutrients on root growth are limited. Here, we investigated the interactive effect between phosphorus (P) and magnesium (Mg) on root growth of Arabidopsis grown in pH-buffered agar medium at different P and Mg levels. The results showed that elongation and deviation of primary roots were directly correlated with the amount of P added to the medium but could be modified by the Mg level, which was related to the root meristem activity and stem-cell division. High P enhanced while low P decreased the tip-focused fluorescence signal of auxin biosynthesis, transport, and redistribution during elongation of primary roots; these effects were greater under low Mg than under high Mg. The altered root growth in response to P and Mg supply was correlated with AUX1, PIN2, and PIN3 mRNA abundance and expression and the accumulation of the protein. Application of either auxin influx inhibitor or efflux inhibitor inhibited the elongation and increased the deviation angle of primary roots, and decreased auxin level in root tips. Furthermore, the auxin-transport mutants aux1-22 and eir1-1 displayed reduced root growth and increased the deviation angle. Our data suggest a profound effect of the combined supply of P and Mg on the development of root morphology in Arabidopsis through auxin signals that modulate the elongation and directional growth of primary root and the expression of root differentiation and development genes.

Magnesium availability regulates the development of root hairs in Arabidopsis thaliana (L.) Heynh.

Root hairs are reported to be plastic in response to nutrient supply, but relatively little is known about their development in response to magnesium (Mg) availability. Here, we showed that development of root hairs of Arabidopsis decreased progressively with increasing Mg supply, which was related to the initiation of new trichoblast files and likelihood of trichoblasts to form hairs. Tip-focused reactive oxygen species (ROS) and cytosolic Ca(2+) concentrations [(Ca(2+) )c] during elongation of root hairs were enhanced under low Mg but decreased under high Mg. Under low Mg, application of diphenylene iodonium (DPI) or BAPTA [1,2-bis(o-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid] blocked the enhanced development of root hairs and the opposite was true when the plants under high Mg were treated with phenazine methosulphate (PMS), methyl viologen (MV) or CaCl2 . Furthermore, Mg availability did not alter root hair growth in rhd2-1 mutant that contains lower levels of ROS and cytosolic [Ca(2+) ]c. Transcriptome data and qPCR results revealed a greater fraction of morphogenetic H-genes, and cell wall organization genes were up-regulated by low Mg but down-regulated by high Mg. Our data suggest a profound effect of Mg supply on the development of root hairs in Arabidopsis, through the characterized Ca(2+) and ROS signals that modulate the elongation of root hairs and the expression of root-hair morphogenetic genes.

Gut Dysbiosis Drives Inflammatory Bowel Disease Through the CCL4L2-VSIR Axis in Glycogen Storage Disease.

Patients with glycogen storage disease type Ib (GSD-Ib) frequently have inflammatory bowel disease (IBD). however, the underlying etiology remains unclear. Herein, this study finds that digestive symptoms are commonly observed in patients with GSD-Ib, presenting as single or multiple scattered deep round ulcers, inflammatory pseudo-polyps, obstructions, and strictures, which differ substantially from those in typical IBD. Distinct microbiota profiling and single-cell clustering of colonic mucosae in patients with GSD are conducted. Heterogeneous oral pathogenic enteric outgrowth induced by GSD is a potent inducer of gut microbiota immaturity and colonic macrophage accumulation. Specifically, a unique population of macrophages with high CCL4L2 expression is identified in response to pathogenic bacteria in the intestine. Hyper-activation of the CCL4L2-VSIR axis leads to increased expression of AGR2 and ZG16 in epithelial cells, which mediates the unique progression of IBD in GSD-Ib. Collectively, the microbiota-driven pathomechanism of IBD is demonstrated in GSD-Ib and revealed the active role of the CCL4L2-VSIR axis in the interaction between the microbiota and colonic mucosal immunity. Thus, targeting gut dysbiosis and/or the CCL4L2-VISR axis may represent a potential therapy for GSD-associated IBD.

Genome sequence of the biocontrol agent Microbacterium barkeri strain 2011-R4.

Microbacterium barkeri strain 2011-R4 is a Gram-positive epiphyte which has been confirmed as a biocontrol agent against several plant pathogens in our previous studies. Here, we present the draft genome sequence of this strain, which was isolated from the rice rhizosphere in Tonglu city, Zhejiang province, China.

Genome sequence of Stenotrophomonas maltophilia RR-10, isolated as an endophyte from rice root.

Stenotrophomonas maltophilia is an endophyte which plays important roles in agricultural production as a plant growth-promoting bacterium. Here, we present the draft genome sequence of strain RR-10, which was isolated from a rice root in a rice field of China.

Genome sequence of the plant pathogen Pseudomonas syringae pv. panici LMG 2367.

Pseudomonas syringae pv. panici is a phytopathogenic bacterium causing brown stripe disease in economically important crops worldwide. Here, we announce the draft genome sequence of Pseudomonas syringae pv. panici LMG2367 to provide further valuable insights for comparison of the pathovars among species Pseudomonas syringae.

Genome sequence of the rice pathogen Pseudomonas fuscovaginae CB98818.

Pseudomonas fuscovaginae is a phytopathogenic bacterium causing bacterial sheath brown rot of cereal crops. Here, we present the draft genome sequence of P. fuscovaginae CB98818, originally isolated from a diseased rice plant in China. The draft genome will aid in epidemiological studies, comparative genomics, and quarantine of this broad-host-range pathogen.

Characteristics of gut microbiota in patients with gastric cancer by surgery, chemotherapy and lymph node metastasis.

BACKGROUND: Gastric cancer (GC) is a malignant gastrointestinal tumor that can result in high mortality. Surgery and chemotherapy are often used for the effective treatment of GC. In addition, lymph node metastasis is a significant factor affecting the therapy of GC. Current researches have revealed that gut microbiota has the potential as biomarkers to distinguish healthy people and GC patients. However, the relationship between surgery, chemotherapy, and lymph node metastasis is still unclear. METHODS: In this study, 16S rRNA sequencing was used to investigate 157 GC fecal samples to identify the role of surgery, chemotherapy, and lymph node metastasis. Immunohistochemical analysis was used to value the expression of Ki67, HER2 in GC patient tissues. RESULTS: There exist some gut microbiotas which can distinguish surgery from non-surgery GC patients, including Enterococcus, Megasphaera, Corynebacterium, Roseburia, and Lachnospira. Differences between lymph node metastasis and chemotherapy in GC patients are not significant. Moreover, we found the abundance of Blautia, Ruminococcus, Oscillospira were related to the expression of Ki67 and the abundance of Prevotella, Lachnospira, Eubacterium, Desulfovibiro were correlated with the expression of HER2. CONCLUSIONS: The choice of treatment has a certain impact on the intestinal flora of patients with gastric cancer. Our research shows that surgery has a great effect on the intestinal flora of patients with gastric cancer. However, there were no significant differences in the characteristics of intestinal flora in patients with gastric cancer whether they received chemotherapy or whether they had lymph node metastasis. In addition, the association of gut microbiota with Ki67 and HER2 indicators is expected to provide the possibility of gut microbiota as a tumor prognostic marker.

Genome sequence of the nonpathogenic Listeria monocytogenes serovar 4a strain M7.

This report presents the complete and annotated genome sequence of the naturally nonpathogenic Listeria monocytogenes serovar 4a strain M7, isolated from cow's milk in Zhejiang province, China.

Genome sequence of the rice-pathogenic bacterium Acidovorax avenae subsp. avenae RS-1.

Acidovorax avenae subsp. avenae is a phytobacterium which is the causative agent of several plant diseases with economic significance. Here, we present the draft genome sequence of strain RS-1, which was isolated from rice shoots in a rice field in China. This strain can cause bacterial stripe of rice.

Genome sequence of the Enterobacter mori type strain, LMG 25706, a pathogenic bacterium of Morus alba L.

Enterobacter mori is a plant-pathogenic enterobacterium responsible for the bacterial wilt of Morus alba L. Here we present the draft genome sequence of the type strain, LMG 25706. To the best of our knowledge, this is the first genome sequence of a plant-pathogenic bacterium in the genus Enterobacter.

Horizontal gene transfer in silkworm, Bombyx mori.

BACKGROUND: The domesticated silkworm, Bombyx mori, is the model insect for the order Lepidoptera, has economically important values, and has gained some representative behavioral characteristics compared to its wild ancestor. The genome of B. mori has been fully sequenced while function analysis of BmChi-h and BmSuc1 genes revealed that horizontal gene transfer (HGT) maybe bestow a clear selective advantage to B. mori. However, the role of HGT in the evolutionary history of B. mori is largely unexplored. In this study, we compare the whole genome of B. mori with those of 382 prokaryotic and eukaryotic species to investigate the potential HGTs. RESULTS: Ten candidate HGT events were defined in B. mori by comprehensive sequence analysis using Maximum Likelihood and Bayesian method combining with EST checking. Phylogenetic analysis of the candidate HGT genes suggested that one HGT was plant-to- B. mori transfer while nine were bacteria-to- B. mori transfer. Furthermore, functional analysis based on expression, coexpression and related literature searching revealed that several HGT candidate genes have added important characters, such as resistance to pathogen, to B. mori. CONCLUSIONS: Results from this study clearly demonstrated that HGTs play an important role in the evolution of B. mori although the number of HGT events in B. mori is in general smaller than those of microbes and other insects. In particular, interdomain HGTs in B. mori may give rise to functional, persistent, and possibly evolutionarily significant new genes.

Auxin modulates the enhanced development of root hairs in Arabidopsis thaliana (L.) Heynh. under elevated CO(2).

Root hairs may play a critical role in nutrient acquisition of plants grown under elevated CO(2) . This study investigated how elevated CO(2) enhanced the development of root hairs in Arabidopsis thaliana (L.) Heynh. The plants under elevated CO(2) (800 µL L(-1)) had denser and longer root hairs, and more H-positioned cells in root epidermis than those under ambient CO(2) (350 µL L(-1)). The elevated CO(2) increased auxin production in roots. Under elevated CO(2) , application of either 1-naphthoxyacetic acid (1-NOA) or N-1-naphthylphthalamic acid (NPA) blocked the enhanced development of root hairs. The opposite was true when the plants under ambient CO(2) were treated with 1-naphthylacetic acid (NAA), an auxin analogue. Furthermore, the elevated CO(2) did not enhance the development of root hairs in auxin-response mutants, axr1-3, and auxin-transporter mutants, axr4-1, aux1-7 and pin1-1. Both elevated CO(2) and NAA application increased expressions of caprice, triptychon and rho-related protein from plants 2, and decreased expressions of werewolf, GLABRA2, GLABRA3 and the transparent testa glabra 1, genes related to root-hair development, while 1-NOA and NPA application had an opposite effect. Our study suggests that elevated CO(2) enhanced the development of root hairs in Arabidopsis via the well-characterized auxin signalling and transport that modulate the initiation of root hairs and the expression of its specific genes.