Journal of Genetics and Genomics

Microbiota-gut-brain axis in autism spectrum disorder

You Yu, Fangqing Zhao

2021, 48(9): 755-762. doi: 10.1016/j.jgg.2021.07.001

Abstract (281) PDF (32)

Abstract:
Extensive studies, largely during the past decade, identify the dynamic and bidirectional interaction between the bacteria resident in the intestines and their host brain along the "microbiota-gut-brain axis". This interaction modulates the development and function of the central nervous system and is implicated in neurological disorders. As a neurodevelopmental disorder, autism spectrum disorder (ASD) is considered a historically defect in the brain. With accumulating evidence showing how the microorganisms modulate neural activities, more and more research is focusing on the role of the gut microbiota in mitigating ASD symptoms and the underlying mechanisms. In this review, we describe the intricate and crucial pathways via which the gut microbiota communicates with the brain, the microbiota-gut-brain axis, and summarize the specific pathways that mediate the crosstalk of the gut microbiota to the brain in ASD.

Innate lymphoid cells and gastrointestinal disease

Ziyu Wang, Jun Wang

2021, 48(9): 763-770. doi: 10.1016/j.jgg.2021.08.004

Abstract (232) PDF (22)

Abstract:
Innate lymphoid cells (ILCs) are a group of innate immune cells, which constitute the first line of defense in the immune system, together with skin and mucous membrane. ILCs also play an important role in maintaining the homeostasis of the body, particularly in the complex and diverse environment of the intestine. ILCs respond to different microenvironments, maintaining homeostasis directly or indirectly through cytokines. As a result, ILCs, with complex and pleiotropic characteristics, are associated with many gastrointestinal diseases. Their ability of transition among those subgroups makes them function as both promoting and inhibiting cells, thus affecting homeostasis and disease progressing to either alleviation or deterioration. With these special characteristics, ILCs theoretically can be used in the new generation of immunotherapy as an alternative and supplement to current tumor therapy. Our review summarizes the characteristics of ILCs with respect to category, function, and the relationship with intestinal homeostasis and gastrointestinal diseases. In addition, potential tumor immunotherapies involving ILCs are also discussed to shed light on the perspectives of immunotherapy.

Altered gut microbiome in FUT2 loss-of-function mutants in support of personalized medicine for inflammatory bowel diseases

Sijing Cheng, Jun Hu, Xianrui Wu, Ji-An Pan, Na Jiao, Yichen Li, Yibo Huang, Xutao Lin, Yifeng Zou, Yuan Chen, Lixin Zhu, Min Zhi, Ping Lan

2021, 48(9): 771-780. doi: 10.1016/j.jgg.2021.08.003

Abstract (323) PDF (37)

Abstract:
The FUT2 loss-of-function mutations are highly prevalent and are associated with inflammatory bowel disease (IBD). To investigate the impact of FUT2 loss-of-function mutation on the gut microbiota in patients with IBD, 81 endoscopically confirmed IBD patients were genotyped and divided into 3 groups:homozygous for functional FUT2 genes (SeSe), with one copy of non-functional FUT2 gene (Sese), or homozygous for non-functional FUT2 genes (sese). Escherichia, which attaches to fucosylated glycoconjugates, was the only abundant genus exhibiting decreased abundance in sese patients. Compared with SeSe or Sese patients, sese patients exhibited higher abundance in CD8⁺ inducing Alistipe and Phascolarctobacterium and Th17 inducing Erysipelotrichaceae UCG-003. Counter-intuitively, butyrate-producing bacteria were more abundant in sese patients. Consistently, metabolomics analysis found higher levels of butyrate in sese patients. Our data support the hypothesis that FUT2 loss-of-function mutation participates in the IBD pathogenesis by decreasing binding sites for adherent bacteria and thus altering the gut microbiota. Decreased abundances of adherent bacteria may allow the overgrowth of bacteria that induce inflammatory T cells, leading to intestinal inflammation. As FUT2 loss-of-function mutations are highly prevalent, the identification of T cell inducing bacteria in sese patients could be valuable for the development of personalized microbial intervention for IBD.

Characteristic dysbiosis in gout and the impact of a uric acid-lowering treatment, febuxostat on the gut microbiota

Suxian Lin, Tao Zhang, Lingxiao Zhu, Kun Pang, Saisai Lu, Xin Liao, Senhong Ying, Lixia Zhu, Xin Xu, Jinyu Wu, Xiaobing Wang

2021, 48(9): 781-791. doi: 10.1016/j.jgg.2021.06.009

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Abstract:
Gut dysbiosis is suggested to play a critical role in the pathogenesis of gout. The aim of our study was to identify the characteristic dysbiosis of the gut microbiota in gout patients and the impact of a commonly used uric acid-lowering treatment, febuxostat on gut microbiota in gout. 16S ribosomal RNA sequencing and metagenomic shotgun sequencing was performed on fecal DNA isolated from 38 untreated gout patients, 38 gout patients treated with febuxostat, and 26 healthy controls. A restriction of gut microbiota biodiversity was detected in the untreated gout patients, and the alteration was partly restored by febuxostat. Biochemical metabolic indexes involved in liver and kidney metabolism were significantly associated with the gut microbiota composition in gout patients. Functional analysis revealed that the gut microbiome of gout patients had an enriched function on carbohydrate metabolism but a lower potential for purine metabolism, which was comparatively enhanced in the febuxostat treated gout patients. A classification microbial model obtained a high mean area under the curve up to 0.973. Therefore, gut dysbiosis characterizings gout could potentially serve as a noninvasive diagnostic tool for gout and may be a promising target of future preventive interventions.

Gut microbiota, inflammation, and molecular signatures of host response to infection

Wanglong Gou, Yuanqing Fu, Liang Yue, Geng-Dong Chen, Xue Cai, Menglei Shuai, Fengzhe Xu, Xiao Yi, Hao Chen, Yi Zhu, Mian-Li Xiao, Zengliang Jiang, Zelei Miao, Congmei Xiao, Bo Shen, Xiaomai Wu, Haihong Zhao, Wenhua Ling, Jun Wang, Yu-Ming Chen, Tiannan Guo, Ju-Sheng Zheng

2021, 48(9): 792-802. doi: 10.1016/j.jgg.2021.04.002

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Abstract:
Gut microbial dysbiosis has been linked to many noncommunicable diseases. However, little is known about specific gut microbiota composition and its correlated metabolites associated with molecular signatures underlying host response to infection. Here, we describe the construction of a proteomic risk score based on 20 blood proteomic biomarkers, which have recently been identified as molecular signatures predicting the progression of the COVID-19. We demonstrate that in our cohort of 990 healthy individuals without infection, this proteomic risk score is positively associated with proinflammatory cytokines mainly among older, but not younger, individuals. We further discover that a core set of gut microbiota can accurately predict the above proteomic biomarkers among 301 individuals using a machine learning model and that these gut microbiota features are highly correlated with proinflammatory cytokines in another independent set of 366 individuals. Fecal metabolomics analysis suggests potential amino acid-related pathways linking gut microbiota to host metabolism and inflammation. Overall, our multi-omics analyses suggest that gut microbiota composition and function are closely related to inflammation and molecular signatures of host response to infection among healthy individuals. These results may provide novel insights into the cross-talk between gut microbiota and host immune system.

Progressive deterioration of the upper respiratory tract and the gut microbiomes in children during the early infection stages of COVID-19

Rong Xu, Pengcheng Liu, Tao Zhang, Qunfu Wu, Mei Zeng, Yingying Ma, Xia Jin, Jin Xu, Zhigang Zhang, Chiyu Zhang

2021, 48(9): 803-814. doi: 10.1016/j.jgg.2021.05.004

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Abstract:
Children are less susceptible to coronavirus disease 2019 (COVID-19), and they have manifested lower morbidity and mortality after infection, for which a multitude of mechanisms may be considered. Whether the normal development of the gut-airway microbiome in children is affected by COVID-19 has not been evaluated. Here, we demonstrate that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection alters the upper respiratory tract and the gut microbiomes in nine children. The alteration of the microbiome is dominated by the genus Pseudomonas, and it sustains for up to 25-58 days in different individuals. Moreover, the patterns of alternation are different between the upper respiratory tract and the gut. Longitudinal investigation shows that the upper respiratory tract and the gut microbiomes are extremely variable among children during the course of COVID-19. The dysbiosis of microbiome persists in 7 of 8 children for at least 19-24 days after discharge from the hospital. Disturbed development of both the gut and the upper respiratory microbiomes and prolonged dysbiosis in these nine children imply possible long-term complications after clinical recovery from COVID-19, such as predisposition to the increased health risk in the post-COVID-19 era.

Carrageenan oligosaccharides and associated carrageenan-degrading bacteria induce intestinal inflammation in germ-free mice

Yeshi Yin, Miaomiao Li, Weizhong Gu, Benhua Zeng, Wei Liu, Liying Zhu, Xionge Pi, Donald A. Primerano, Hongwei D. Yu, Hong Wei, Guangli Yu, Xin Wang

2021, 48(9): 815-824. doi: 10.1016/j.jgg.2021.08.001

Abstract (174) PDF (14)

Abstract:
Carrageenans (CGNs) are widely used in foods and pharmaceuticals although their safety remains controversial. To investigate the effects of CGNs and CGN-degrading bacteria in the human colon, we screened for CGN degradation by human fecal microbiota, and for inflammatory response to CGNs and/or CGN-degrading bacteria in germ free mice. Thin-layer chromatography indicated that high molecular weight (MW) CGNs (≥ 100 kDa) remained undegraded in the presence of human fecal microbiota, whereas low MW CGNs, i.e., κ-carrageenan oligosaccharides (KCO,~4.5 kDa) were degraded when exposed to seven of eight human fecal samples, although sulfate groups were not removed during degradation. Bacteroides xylanisolvens and Escherichia coli isolates from fecal samples apparently degraded KCO synergistically, with B. xylanisolvens serving as the primary degrader. Combined treatment of KCO with KCO-degrading bacteria led to greater pro-inflammatory effects in the colon and rectum of germ-free mice than either KCO or bacteria alone. Similarly, p-p38-, CD3-, and CD79a-positive immune cells were more abundant in combined treatment group mice than in either single treatment group. Our study shows that KCO-degrading bacteria and the low MW products of KCO can promote proinflammatory effects in mice, and represent two key markers for evaluating CGN safety in foods or medicines.

Comparative study of gut microbiota from captive and confiscated-rescued wild pangolins

Chunbing Liu, Jingyang Hu, Yajiang Wu, David M. Irwin, Wu Chen, Zhigang Zhang, Li Yu

2021, 48(9): 825-835. doi: 10.1016/j.jgg.2021.07.009

Abstract (255) PDF (13)

Abstract:
Pangolins are among the most critically endangered animals due to widespread poaching and worldwide trafficking. Captive breeding is considered to be one way to protect them and increase the sizes of their populations. However, comparative studies of captive and wild pangolins in the context of gut microbiota are rare. Here, the gut microbiome of captive and confiscated-rescued wild pangolins is compared, and the effects of different periods of captivity and captivity with and without antibiotic treatment are considered. We show that different diets and periods of captivity, as well as the application of antibiotic therapy, can alter gut community composition and abundance in pangolins. Compared to wild pangolins, captive pangolins have an increased capacity for chitin and cellulose/hemicellulose degradation, fatty acid metabolism, and short-chain fatty acid synthesis, but a reduced ability to metabolize exogenous substances. In addition to increasing the ability of the gut microbiota to metabolize nutrients in captivity, captive breeding imposes some risks for survival by resulting in a greater abundance of antibiotic resistance genes and virulence factors in captive pangolins than in wild pangolins. Our study is important for the development of guidelines for pangolin conservation, including health assessment, disease prevention, and rehabilitation of wild pangolin populations.

The rice histone methylation regulates hub species of the root microbiota

Zhiyao Lv, Rui Dai, Haoran Xu, Yongxin Liu, Bo Bai, Ying Meng, Haiyan Li, Xiaofeng Cao, Yang Bai, Xianwei Song, Jingying Zhang

2021, 48(9): 836-843. doi: 10.1016/j.jgg.2021.06.005

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Abstract:
Plants have a close relationship with their root microbiota, which comprises a complex microbial network. Histone methylation is an important epigenetic modification influencing multiple plant traits; however, little is known about the role of plant histone methylation in the assembly and network structure of the root microbiota. In this study, we established that the rice (Oryza sativa) histone methylation regulates the structure and composition of the root microbiota, especially the hub species in the microbial network. DJ-jmj703 (defective in histone H3K4 demethylation) and ZH11-sdg714 (defective in H3K9 methylation) showed significant different root microbiota compared with the corresponding wild types at the phylum and family levels, with a consistent increase in the abundance of Betaproteobacteria and a decrease in the Firmicutes. In the root microbial network, 35 of 44 hub species in the top 10 modules in the tested field were regulated by at least one histone methylation-related gene. These observations establish that the rice histone methylation plays a pivotal role in regulating the assembly of the root microbiota, providing insights into the links between plant epigenetic regulation and root microbiota.

TaxonKit: A practical and efficient NCBI taxonomy toolkit

Wei Shen, Hong Ren

2021, 48(9): 844-850. doi: 10.1016/j.jgg.2021.03.006

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Abstract:
The National Center for Biotechnology Information (NCBI) Taxonomy is widely applied in biomedical and ecological studies. Typical demands include querying taxonomy identifier (TaxIds) by taxonomy names, querying complete taxonomic lineages by TaxIds, listing descendants of given TaxIds, and others. However, existed tools are either limited in functionalities or inefficient in terms of runtime. In this work, we present TaxonKit, a command-line toolkit for comprehensive and efficient manipulation of NCBI Taxonomy data. TaxonKit comprises seven core subcommands providing functions, including TaxIds querying, listing, filtering, lineage retrieving and reformatting, lowest common ancestor computation, and TaxIds change tracking. The practical functions, competitive processing performance, scalability with different scales of datasets and good accessibility can facilitate taxonomy data manipulations. TaxonKit provides free access under the permissive MIT license on GitHub, Brewsci, and Bioconda. The documents are also available at https://bioinf.shenwei.me/taxonkit/.

A powerful adaptive microbiome-based association test for microbial association signals with diverse sparsity levels

Han Sun, Xiaoyun Huang, Lingling Fu, Ban Huo, Tingting He, Xingpeng Jiang

2021, 48(9): 851-859. doi: 10.1016/j.jgg.2021.08.002

Abstract (153) PDF (11)

Abstract:
The dysbiosis of microbiome may have negative effects on a host phenotype. The microbes related to the host phenotype are regarded as microbial association signals. Recently, statistical methods based on microbiome-phenotype association tests have been extensively developed to detect these association signals. However, the currently available methods do not perform well to detect microbial association signals when dealing with diverse sparsity levels (i.e., sparse, low sparse, non-sparse). Actually, the real association patterns related to different host phenotypes are not unique. Here, we propose a powerful and adaptive microbiome-based association test to detect microbial association signals with diverse sparsity levels, designated as MiATDS. In particular, we define probability degree to measure the associations between microbes and the host phenotype and introduce the adaptive weighted sum of powered score tests by considering both probability degree and phylogenetic information. We design numerous simulation experiments for the task of detecting association signals with diverse sparsity levels to prove the performance of the method. We find that type I error rates can be well-controlled and MiATDS shows superior effciency on the power. By applying to real data analysis, MiATDS displays reliable practicability too. The R package is available at https://github.com/XiaoyunHuang33/MiATDS.

An efficient metatranscriptomic approach for capturing RNA virome and its application to SARS-CoV-2

Yao Men, Liwen Xiao, Wenbing Chen, Fangqing Zhao, Xiang Zhao

2021, 48(9): 860-862. doi: 10.1016/j.jgg.2021.08.005

Abstract (218) PDF (34)

Abstract:

EVenn: Easy to create repeatable and editable Venn diagrams and Venn networks online

Tong Chen, Haiyan Zhang, Yu Liu, Yong-Xin Liu, Luqi Huang

2021, 48(9): 863-866. doi: 10.1016/j.jgg.2021.07.007

Abstract (700) PDF (67)

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2021 Vol. 48, No. 9