Gut microbiome and human health under the space environment

The gut microbiome is well recognized to have a pivotal role in regulation of the health and behaviour of the host, affecting digestion, metabolism, immunity, and has been linked to changes in bones, muscles and the brain, to name a few. However, the impact of microgravity environment on gut bacteria is not well understood. In space environments, astronauts face several health issues including stress, high iron diet, radiation and being in a closed system during extended space missions. Herein, we discuss the role of gut bacteria in the space environment, in relation to factors such as microgravity, radiation and diet. Gut bacteria may exact their effects by synthesis of molecules, their absorption, and through physiological effects on the host. Moreover we deliberate the role of these challenges in the dysbiosis of the human microbiota and possible dysregulation of the immune system.     

Gut microbiome and cancer immunotherapy

Gut microbiome has received significant attention for its influences on a variety of host functions, especially immune modulation. With the next-generation sequencing methodologies, more knowledge is gathered about gut microbiome and its irreplaceable role in keeping the balance between human health and diseases is figured out. Immune checkpoint inhibitors (ICIs) are one of the most innovational cancer immunotherapies across cancer types and significantly expand the therapeutic options of cancer patients. However, a proportion of patients show no effective responses or develop immune-related adverse events when responses do occur. More important, it is demonstrated that the therapeutic response or treatment-limiting toxicity of cancer immunotherapy can be ameliorated or diminished by gut microbiome modulation. In this review, we first introduce the relationship between gut microbiome and cancer immunotherapy. And then, we expound the impact of gut microbiome on efficacy and toxicity of cancer immunotherapy. Further, we review approaches to manipulating gut microbiome to regulate response to ICIs. Finally, we discuss the current challenges and propose future directions to improve cancer immunotherapy via gut microbiome manipulation.     

Gut microbiome composition is linked to whole grain-induced immunological improvements

The involvement of the gut microbiota in metabolic disorders, and the ability of whole grains to affect both host metabolism and gut microbial ecology, suggest that some benefits of whole grains are mediated through their effects on the gut microbiome. Nutritional studies that assess the effect of whole grains on both the gut microbiome and human physiology are needed. We conducted a randomized cross-over trial with four-week treatments in which 28 healthy humans consumed a daily dose of 60 g of whole-grain barley (WGB), brown rice (BR), or an equal mixture of the two (BR+WGB), and characterized their impact on fecal microbial ecology and blood markers of inflammation, glucose and lipid metabolism. All treatments increased microbial diversity, the Firmicutes/Bacteroidetes ratio, and the abundance of the genus Blautia in fecal samples. The inclusion of WGB enriched the genera Roseburia, Bifidobacterium and Dialister, and the species Eubacterium rectale, Roseburia faecis and Roseburia intestinalis. Whole grains, and especially the BR+WGB treatment, reduced plasma interleukin-6 (IL-6) and peak postprandial glucose. Shifts in the abundance of Eubacterium rectale were associated with changes in the glucose and insulin postprandial response. Interestingly, subjects with greater improvements in IL-6 levels harbored significantly higher proportions of Dialister and lower abundance of Coriobacteriaceae. In conclusion, this study revealed that a short-term intake of whole grains induced compositional alterations of the gut microbiota that coincided with improvements in host physiological measures related to metabolic dysfunctions in humans.     

不同保存液和保存期限下肠道微生物组的变化

肠道菌群与人体健康的关系密切,通过检测肠道菌群可以获得有关健康的信息。新鲜粪便不易获得,很难做到快速低温冷冻,在进行标准化和大规模人群采样时,可用于常温条件下采集和保存样本的保存液可以弥补采集样本数量多、地域分布广、现场采样条件多样、工作量大、运输条件差等条件不足。本研究招募了5名健康志愿者,采集他们的粪便样本后,通过对比不同市售微生物样本采集常温保存液对新鲜粪便样本的影响,评估了各类保存液的保存效果。在室温下把粪便放置于5种保存液,在第0、1、3、7、15、30天提取元基因组DNA,进行16S rRNA V3–V4区高通量测序,来分析不同保存液,在不同时间段对肠道菌群组成的影响。结果显示,不同保存液对肠道菌群的影响存在差异,与对照组相比,不同保存液对样本中的OUT数量影响不大;保存液A、B和C在菌群构成上更接近对照组,保存液D会明显改变肠道菌群组成,使放线菌门(Actinobacteria)和厚壁菌门(Firmicutes)增加;随着时间延长,各类保存液都有降低菌群多样性趋势,保存液E降低菌群多样性更明显;第30天时,5种保存液都会改变肠道菌群构成;肠道菌群组成存在个体差异,是影响各...     

Gut microbiome in tumorigenesis and therapy of colorectal cancer

Colorectal cancer (CRC) is the malignant tumor with the highest incidence in the digestive system, and the gut microbiome plays a crucial role in CRC tumorigenesis and therapy. The gastrointestinal tract is the organ harboring most of the microbiota in humans. Changes in the gut microbiome in CRC patients suggest possible host–microbe interactions, thereby hinting the potential tumorigenesis, which provides new perspective for preventing, diagnosing, or treating CRC. In this review, we discuss the effects of gut microbiome dysbiosis on CRC, and reveal the mechanisms by which gut microbiome dysbiosis leads to CRC. Gut microbiome modulation with the aim to reverse the established gut microbial dysbiosis is a novel strategy for the prevention and treatment of CRC. In addition, this review summarizes that probiotic antagonize CRC tumorigenesis by protecting intestinal barrier function, inhibiting cancer cell proliferation, resisting oxidative stress, and enhancing host immunity. Finally, we highlight clinical applications of the gut microbiome, such as gut microbiome analysis-based biomarker screening and prediction, and microbe modulation-based CRC prevention, treatment enhancement, and treatment side effect reduction. This review provides the reference for the clinical application of gut microbiome in the prevention and treatment of CRC.     

基于机器学习的肠道菌群数据建模与分析研究综述

人体肠道菌群与人类的健康和疾病存在密切关系,对肠道菌群的宏基因组数据进行建模和分析,在疾病预测及诊断相关领域科学研究和社会应用方面均具有重要意义。本文从大数据分析和机器学习的角度,对人体肠道菌群数据的建模、分析和预测算法的原理、过程以及典型研究应用实例进行综述,以期推动肠道菌群分析相关研究发展以及探索结合机器学习算法进行肠道菌群分析的有效方式,同时也为开发基于肠道菌群数据的新型诊疗手段提供借鉴,推动我国精准医疗事业发展。     

Gut microbiome dysbiosis and honeybee health

Since a few decades, apiculture is facing important economic losses worldwide with general major consequences in many areas of agriculture. A strong attention has been paid towards the phenomenon named Colony Collapse Disorder in which colonies suddenly disappear with no clear explanations. Honeybee colonies can be affected by abiotic factors, such as environmental pollution or insecticide applications for agricultural purposes. Also biotic stresses cause colony losses, including bacterial (e.g. Paenibacillus larvae) and fungal (e.g. Ascosphaera apis) pathogens, microsporidia (e.g. Nosema apis), parasites (i.e. Varroa destructor) and several viruses. In the light of recent research, intestinal dysbiosis, considered as the relative disproportion of the species within the native microbiota, has shown to affect human and animal health. In arthropods, alteration of the gut microbial climax community has been shown to be linked to health and fitness disequilibrium, like in the medfly Ceratitis capitata for which low mate competitiveness is determined by a gut microbial community imbalance. According to these observations, it is possible to hypothesize that dysbiosis may have a role in disease occurrence also in honeybees. Here we aim to discuss the current knowledge on dysbiosis in the honeybee and its relation with honeybee health by reviewing the investigations of the microbial diversity associated to honeybees and the recent experiments performed to control bee diseases by microbial symbionts. We conclude that, despite the importance of a good functionality of the associated microbiota in preserving insect health has been proved, the mechanisms involved in honeybee gut dysbiosis are still unknown. Accurate in vitro, in vivo and in field investigations are required under healthy, diseased and stressed conditions for the host.     

Gut microbiome of multiple sclerosis patients and paired household healthy controls reveal associations with disease risk and course

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Gut microbiome of migratory shorebirds: Current status and future perspectives

Migratory shorebirds have many unique life history characteristics, such as long‐distance travel between breeding sites, stopover sites, and wintering sites. The physiological challenges for migrant energy requirement and immunity may affect their gut microbiome community. Here, we reviewed the specific features (e.g., relatively high proportion of Corynebacterium and Fusobacterium) in the gut microbiome of 18 migratory shorebirds, and the factors (e.g., diet, migration, environment, and phylogeny) affecting the gut microbiome. We discussed possible future studies of the gut microbiome in migratory shorebirds, including the composition and function of the spatial‐temporal gut microbiome, and the potential contributions made by the gut microbiome to energy requirement during migration.     

Age‐related changes in the marmoset gut microbiome

The gut microbiome is known to play a significant role in human health but its role in aging remains unclear. The objective of this study was to compare the gut microbiome composition between young adult and geriatric non‐human primates (marmosets) as a model of human health and disease. Stool samples were collected from geriatric (8+ years) and young adult males (2–5 years). Stool 16S ribosomal RNA V4 sequences were amplified and sequenced on the Illumina MiSeq platform. Sequences were clustered into operational taxonomic units and classified via Mothur's Bayesian classifier referenced against the Greengenes database. A total of 10 young adult and 10 geriatric marmosets were included. Geriatric marmosets had a lower mean Shannon diversity compared with young marmosets (3.15 vs. 3.46; p = 0.0191). Geriatric marmosets had a significantly higher mean abundance of Proteobacteria (0.22 vs. 0.09; p = 0.0233) and lower abundance of Firmicutes (0.15 vs. 0.19; p = 0.0032) compared with young marmosets. Geriatric marmosets had a significantly higher abundance of Succinivibrionaceae (0.16 vs. 0.01; p = 0.0191) and lower abundance of Porphyromonadaceae (0.07 vs. 0.11; p = 0.0494). In summary, geriatric marmosets had significantly altered microbiome diversity and composition compared with young adult marmosets. Further studies are needed to test microbiome‐targeted therapies to improve healthspan and lifespan.     

慢性阻塞性肺疾病患者肠道微生物组成及基因功能分析

探讨慢性阻塞性肺疾病（COPD）患者肠道微生物组成、丰度及差异基因功能变化。

收集我院呼吸科10例确诊COPD患者（COPD组）和10例对照受试者（对照组）粪便样品进行宏基因组高通量测序分析。

PCA分析组间比较发现2组研究对象粪便样品微生物群落差异大,具有可比性。物种组成分析显示：对照组粪便样品中高度富集的菌科主要包括毛螺菌科、理研菌科、韦荣球菌科、优杆菌科、臭杆菌科、氨基酸球菌科、乳杆菌科等,属层面富集的主要包括罗斯菌属、胃瘤球菌属、小杆菌属、真杆菌属、拟杆菌属、粪球菌属、双歧杆菌属等;COPD组粪便样品富集菌群主要包括紫单胞菌科、Selenomonadaceae、巨单胞菌属和韦荣球菌属。物种多样性分析与对照组相比,COPD组多样性更低,差异有统计学意义（W = 87,P = 0.0039）。物种相关性网络图分析显示与其他门类菌群相比,拟杆菌门、厚壁菌门、变形菌门与其他物种的关联性最强（size = 52.07、18.87、14.01）。组间差异基因进行GO功能显著性富集分析,差异基因均富集在如细胞学过程、刺激应答、生物学黏附及调节、代谢过程及信号通路等。KEGG功能显著性富集分析显示差异基因主要富集途径包括代谢途径、次生代谢物合成、淀粉和蔗糖的合成、抗生素的合成等。

COPD患者肠道内存在菌群及基因功能失调。

     

Feasibility of fecal microbiota transplantation via oral gavage to safely alter gut microbiome composition in marmosets

Disruption of microbial communities within human hosts has been associated with infection, obesity, cognitive decline, cancer risk and frailty, suggesting that microbiome-targeted therapies may be an option for improving healthspan and lifespan. The objectives of this study were to determine the feasibility of delivering fecal microbiota transplants (FMTs) to marmosets via oral gavage and to evaluate if alteration of the gut microbiome post-FMT could be achieved. This was a prospective study of marmosets housed at the Barshop Institute for Longevity and Aging Studies in San Antonio, Texas. Eligible animals included healthy young adult males (age 2–5 years) with no recent medication use. Stool from two donors was combined and administered in 0.5 ml doses to five young recipients once weekly for 3 weeks. Safety outcomes and alterations in the gut microbiome composition via 16S ribosomal RNA sequencing were compared at baseline and monthly up to 6 months post-FMT. Overall, significant differences in the percent relative abundance was seen in FMT recipients at the phylum and family levels from baseline to 1 month and baseline to 6 months post-FMT. In permutational multivariate analysis of variance analyses, treatment status (donor vs. recipient) (p = .056) and time course (p = .019) predicted β diversity (p = .056). The FMT recipients did not experience any negative health outcomes over the course of the treatment. FMT via oral gavage was safe to administer to young adult marmosets. The marmoset microbiome may be altered by FMT; however, progressive changes in the microbiome are strongly driven by the host and its baseline microbiome composition.     

Measuring the gut microbiome in birds: Comparison of faecal and cloacal sampling

The gut microbiomes of birds and other animals are increasingly being studied in ecological and evolutionary contexts. Numerous studies on birds and reptiles have made inferences about gut microbiota using cloacal sampling; however, it is not known whether the bacterial community of the cloaca provides an accurate representation of the gut microbiome. We examined the accuracy with which cloacal swabs and faecal samples measure the microbiota in three different parts of the gastrointestinal tract (ileum, caecum, and colon) using a case study on juvenile ostriches, Struthio camelus, and high‐throughput 16S rRNA sequencing. We found that faeces were significantly better than cloacal swabs in representing the bacterial community of the colon. Cloacal samples had a higher abundance of Gammaproteobacteria and fewer Clostridia relative to the gut and faecal samples. However, both faecal and cloacal samples were poor representatives of the microbial communities in the caecum and ileum. Furthermore, the accuracy of each sampling method in measuring the abundance of different bacterial taxa was highly variable: Bacteroidetes was the most highly correlated phylum between all three gut sections and both methods, whereas Actinobacteria, for example, was only strongly correlated between faecal and colon samples. Based on our results, we recommend sampling faeces, whenever possible, as this sample type provides the most accurate assessment of the colon microbiome. The fact that neither sampling technique accurately portrayed the bacterial community of the ileum nor the caecum illustrates the difficulty in noninvasively monitoring gut bacteria located further up in the gastrointestinal tract. These results have important implications for the interpretation of avian gut microbiome studies.     

Gut microbiota derived metabolites in cardiovascular health and disease

Trillions of microbes inhabit the human gut, not only providing nutrients and energy to the host from the ingested food, but also producing metabolic bioactive signaling molecules to maintain health and elicit disease, such as cardiovascular disease (CVD). CVD is the leading cause of mortality worldwide. In this review, we presented gut microbiota derived metabolites involved in cardiovascular health and disease, including trimethylamine-N-oxide (TMAO), uremic toxins, short chain fatty acids (SCFAs), phytoestrogens, anthocyanins, bile acids and lipopolysaccharide. These gut microbiota derived metabolites play critical roles in maintaining a healthy cardiovascular function, and if dysregulated, potentially causally linked to CVD. A better understanding of the function and dynamics of gut microbiota derived metabolites holds great promise toward mechanistic predicative CVD biomarker discoveries and precise interventions.     

Overview of the rules of the microbial engagement in the gut microbiome: a step towards microbiome therapeutics

Human gut microbiome is a diversified, resilient, immuno-stabilized, metabolically active and physiologically essential component of the human body. Scientific explorations have been made to seek in-depth information about human gut microbiome establishment, microbiome functioning, microbiome succession, factors influencing microbial community dynamics and the role of gut microbiome in health and diseases. Extensive investigations have proposed the microbiome therapeutics as a futuristic medicine for various physiological and metabolic disorders. A comprehensive outlook of microbial colonization, host–microbe interactions, microbial adaptation, commensal selection and immuno-survivability is still required to catalogue the essential genetic and physiological features for the commensal engagement. Evolution of a structured human gut microbiome relies on the microbial flexibility towards genetic, immunological and physiological adaptation in the human gut. Key features for commensalism could be utilized in developing tailor-made microbiome-based therapy to overcome various physiological and metabolic disorders. This review describes the key genetics and physiological traits required for host–microbe interaction and successful commensalism to institute a human gut microbiome.     

Gut dysbacteriosis and intestinal disease: mechanism and treatment

The gut microbiome functions like an endocrine organ, generating bioactive metabolites, enzymes or small molecules that can impact host physiology. Gut dysbacteriosis is associated with many intestinal diseases including (but not limited to) inflammatory bowel disease, primary sclerosing cholangitis-IBD, irritable bowel syndrome, chronic constipation, osmotic diarrhoea and colorectal cancer. The potential pathogenic mechanism of gut dysbacteriosis associated with intestinal diseases includes the alteration of composition of gut microbiota as well as the gut microbiota–derived signalling molecules. The many correlations between the latter and the susceptibility for intestinal diseases has placed a spotlight on the gut microbiome as a potential novel target for therapeutics. Currently, faecal microbial transplantation, dietary interventions, use of probiotics, prebiotics and drugs are the major therapeutic tools utilized to impact dysbacteriosis and associated intestinal diseases. In this review, we systematically summarized the role of intestinal microbiome in the occurrence and development of intestinal diseases. The potential mechanism of the complex interplay between gut dysbacteriosis and intestinal diseases, and the treatment methods are also highlighted.     

Deciphering microbial interactions in synthetic human gut microbiome communities

The ecological forces that govern the assembly and stability of the human gut microbiota remain unresolved. We developed a generalizable model‐guided framework to predict higher‐dimensional consortia from time‐resolved measurements of lower‐order assemblages. This method was employed to decipher microbial interactions in a diverse human gut microbiome synthetic community. We show that pairwise interactions are major drivers of multi‐species community dynamics, as opposed to higher‐order interactions. The inferred ecological network exhibits a high proportion of negative and frequent positive interactions. Ecological drivers and responsive recipient species were discovered in the network. Our model demonstrated that a prevalent positive and negative interaction topology enables robust coexistence by implementing a negative feedback loop that balances disparities in monospecies fitness levels. We show that negative interactions could generate history‐dependent responses of initial species proportions that frequently do not originate from bistability. Measurements of extracellular metabolites illuminated the metabolic capabilities of monospecies and potential molecular basis of microbial interactions. In sum, these methods defined the ecological roles of major human‐associated intestinal species and illuminated design principles of microbial communities.     

Dynamic Modulation of the Gut Microbiota and Metabolome by Bacteriophages in a Mouse Model

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Genetic manipulation of gut microbes enables single-gene interrogation in a complex microbiome

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