Background Checkpoint-blockade immunotherapy targeting programmed cell death protein 1 (PD-1) has recently shown promising efficacy in hepatocellular carcinoma (HCC). However, the factors affecting and predicting the response to anti-PD-1 immunotherapy in HCC are still unclear. Herein, we report the dynamic variation characteristics and specificities of the gut microbiome during anti-PD-1 immunotherapy in HCC using metagenomic sequencing. Results Fecal samples from patients responding to immunotherapy showed higher taxa richness and more gene counts than those of non-responders. For dynamic analysis during anti-PD-1 immunotherapy, the dissimilarity of beta diversity became prominent across patients as early as Week 6. In non-responders, Proteobacteria increased from Week 3, and became predominant at Week 12. Twenty responder-enriched species, including Akkermansia muciniphila and Ruminococcaceae spp., were further identified. The related functional genes and metabolic pathway analysis, such as carbohydrate metabolism and methanogenesis, verified the potential bioactivities of responder-enriched species. Conclusions Gut microbiome may have a critical impact on the responses of HCC patients treated with anti-PD-1 immunotherapy. The dynamic variation characteristics of the gut microbiome may provide early predictions of the outcomes of immunotherapy in HCC, which is critical for disease-monitoring and treatment decision-making. Electronic supplementary material The online version of this article (10.1186/s40425-019-0650-9) contains supplementary material, which is available to authorized users.

BackgroundThe assessment and characterization of the gut microbiome has become a focus of research in the area of human autoimmune diseases. Ankylosing spondylitis is an inflammatory autoimmune disease and evidence showed that ankylosing spondylitis may be a microbiome-driven disease.ResultsTo investigate the relationship between the gut microbiome and ankylosing spondylitis, a quantitative metagenomics study based on deep shotgun sequencing was performed, using gut microbial DNA from 211 Chinese individuals. A total of 23,709 genes and 12 metagenomic species were shown to be differentially abundant between ankylosing spondylitis patients and healthy controls. Patients were characterized by a form of gut microbial dysbiosis that is more prominent than previously reported cases with inflammatory bowel disease. Specifically, the ankylosing spondylitis patients demonstrated increases in the abundance of Prevotella melaninogenica, Prevotella copri, and Prevotella sp. C561 and decreases in Bacteroides spp. It is noteworthy that the Bifidobacterium genus, which is commonly used in probiotics, accumulated in the ankylosing spondylitis patients. Diagnostic algorithms were established using a subset of these gut microbial biomarkers.ConclusionsAlterations of the gut microbiome are associated with development of ankylosing spondylitis. Our data suggest biomarkers identified in this study might participate in the pathogenesis or development process of ankylosing spondylitis, providing new leads for the development of new diagnostic tools and potential treatments.Electronic supplementary materialThe online version of this article (doi:10.1186/s13059-017-1271-6) contains supplementary material, which is available to authorized users.

The human gut microbiota varies considerably among world populations due to a variety of factors including genetic background, diet, cultural habits and socioeconomic status. Here we characterized 110 healthy Mongolian adults gut microbiota by shotgun metagenomic sequencing and compared the intestinal microbiome among Mongolians, the Hans and European cohorts. The results showed that the taxonomic profile of intestinal microbiome among cohorts revealed the Actinobaceria and Bifidobacterium were the key microbes contributing to the differences among Mongolians, the Hans and Europeans at the phylum level and genus level, respectively. Metagenomic species analysis indicated that Faecalibacterium prausnitzii and Coprococcus comeswere enrich in Mongolian people which might contribute to gut health through anti-inflammatory properties and butyrate production, respectively. On the other hand, the enriched genus Collinsella, biomarker in symptomatic atherosclerosis patients, might be associated with the high morbidity of cardiovascular and cerebrovascular diseases in Mongolian adults. At the functional level, a unique microbial metabolic pathway profile was present in Mongolian's gut which mainly distributed in amino acid metabolism, carbohydrate metabolism, energy metabolism, lipid metabolism, glycan biosynthesis and metabolism. We can attribute the specific signatures of Mongolian gut microbiome to their unique genotype, dietary habits and living environment.The gut microbiota (GM) is recognized as a human co-evolutionary partner that facilitates nutritional acquisition and immune modulation, and helps maintain host homeostasis in response to profound lifestyle changes 1-3 . Researchers have delineated the structural and functional configurations of gut metagenomes in different world populations by next generation sequencing [4][5][6][7] . The functional GM layout may represent host genotypic characteristics and reflect an adaptive ecosystem response to the host diet and cultural habits.The microbiota of the Mongolian population is of particular interest to researchers, because Mongolia encompasses a uniquely wide range of environmental conditions and ethnogeographical cohorts. Moreover, the Mongol Empire was the world's largest contiguous empire, exerted a major influence that greatly enhanced the cultural exchange between Mongolia and Europe that took place during the Middle Ages, when Mongolians intermingled with various populations in the Eurasian continent. Importantly, it has been reported that genetically, more than 20% people in the world are related to Mongolians 8 . Mongolians living in pastureland, such as Khentii Province, maintains a traditional nomadic lifestyle (Fig. 1A), whereas those in urban areas, such as Ulan Bator (the capital of Mongolia) and TUW Province (the suburbs of the capital), have adopted an urban lifestyle due to rapid modernization and economic development. Chinese Mongolians living in Hohhot and Xilingol have inter-married with ethic Han Chinese, which may generate some differences fr...

Intestinal microbiota plays a crucial role in immune development and disease progression in mammals from birth onwards. The gastrointestinal tract of newborn mammals is rapidly colonized by microbes with tremendous biomass and diversity. Understanding how this complex of segmental communities evolves in different gastrointestinal sites over time has great biological significance and medical implications. However, most previous reports examining intestinal microbiota have focused on fecal samples, a strategy that overlooks the spatial microbial dynamics in different intestinal segments. Using intestinal digesta from six intestinal segments (duodenum, jejunum, ileum, cecum, colon and rectum) of newborn piglets, we herein conducted a large-scale 16S rRNA gene sequencing-based study to characterize the segmental dynamics of porcine gut microbiota at eight postnatal intervals (days 1, 7, 14, 21, 28, 35, 120 and 180). A total of 4,465 OTUs were obtained and showed that the six intestinal segments could be divided into three parts; in the duodenum-jejunum section, the most abundant genera included Lactobacillus and Bacteroides ; in the ileum, Fusobacterium and Escherichia ; and in the cecum-rectum section, Prevotella . Although the microbial communities of the piglets were similar among the six intestinal segments on postnatal day 1, they evolved and quickly differentiated at later intervals. An examination of time-dependent alterations in the dominant microbes revealed that the microbiome in the large intestine was very different from and much more stable than that in the small intestine. The gut microbiota in newborn piglets exhibited apparent temporal and spatial variations in different intestinal segments. The database of gut microbes in piglets could be a referable resource for future studies on mammalian gut microbiome development in early host growth phases.

Life-cycle stages of the microsporidia Nosema bombycis, the pathogen causing silkworm pebrine, were separated and purified by an improved method of Percoll-gradient centrifugation. Soluble protein fractions of late sporoblasts (spore precursor cells) and mature spores were analysed by two-dimensional polyacrylamide gel electrophoresis (2D-PAGE). Protein spots were recovered from gels and analysed by mass spectrometry. The most abundant differential protein spot was identified by database search to be a hypothetical spore wall protein. Using immunoelectron microscopy, we demonstrated that HSWP5 is localized to the exospore of mature spores and renamed it as spore wall protein 5 (NbSWP5). Further spore phagocytosis assays indicated that NbSWP5 can protect spores from phagocytic uptake by cultured insect cells. This spore wall protein may function both for structural integrity and in modulating host cell invasion.