Integrative analysis reveals associations between oral microbiota dysbiosis and host genetic and epigenetic aberrations in oral cavity squamous cell carcinoma.

Dysbiosis of the human oral microbiota has been reported to be associated with oral cavity squamous cell carcinoma (OSCC) while the host-microbiota interactions with respect to the potential impact of pathogenic bacteria on host genomic and epigenomic abnormalities remain poorly studied. In this study, the mucosal bacterial community, host genome-wide transcriptome and DNA CpG methylation were simultaneously profiled in tumors and their adjacent normal tissues of OSCC patients. Significant enrichment in the relative abundance of seven bacteria species (Fusobacterium nucleatum, Treponema medium, Peptostreptococcus stomatis, Gemella morbillorum, Catonella morbi, Peptoanaerobacter yurli and Peptococcus simiae) were observed in OSCC tumor microenvironment. These tumor-enriched bacteria formed 254 positive correlations with 206 up-regulated host genes, mainly involving signaling pathways related to cell adhesion, migration and proliferation. Integrative analysis of bacteria-transcriptome and bacteria-methylation correlations identified at least 20 dysregulated host genes with inverted CpG methylation in their promoter regions associated with enrichment of bacterial pathogens, implying a potential of pathogenic bacteria to regulate gene expression, in part, through epigenetic alterations. An in vitro model further confirmed that Fusobacterium nucleatum might contribute to cellular invasion via crosstalk with E-cadherin/ß-catenin signaling, TNFα/NF-κB pathway and extracellular matrix remodeling by up-regulating SNAI2 gene, a key transcription factor of epithelial-mesenchymal transition (EMT). Our work using multi-omics approaches explored complex host-microbiota interactions and provided important insights into genetic and functional basis in OSCC tumorigenesis, which may serve as a precursor for hypothesis-driven study to better understand the causational relationship of pathogenic bacteria in this deadly cancer.

Development of the early-life gut microbiome and associations with eczema in a prospective Chinese cohort.

IMPORTANCE: Eczema is a major allergic disease in children, which is particularly prevalent in Chinese children during their first year of life. In this study, we showed that alterations in the infant gut microbiota precede the development of eczema in a prospective Chinese cohort. In particular, we discovered enrichments of the genera Clostridium sensu stricto 1 and Finegoldia in the cases at 3 and 1 month of age, respectively, which may represent potential targets for intervention to prevent eczema. Besides, we identified a depletion of Bacteroides from 1 to 6 months of age and an enrichment of Clostridium sensu stricto 1 at 3 months in the eczema cases, patterns also observed in C-section-born infants within the same time frames, providing first evidence to support a role of the gut microbiota in previously reported associations between C-section and increased risk of eczema in infancy.

The effect of Andrographis paniculata water extract on palliative management of metastatic esophageal squamous cell carcinoma-A phase II clinical trial.

Patients with metastatic esophageal squamous cell carcinoma (ESCC) have a grave prognosis with limited life expectancy. Here, a phase II clinical trial was conducted to investigate the effect of Andrographis paniculata (AP) on the palliative care of patients with metastatic ESCC. Patients with metastatic or locally advanced ESCC deemed unfit for surgery, and who have already completed palliative chemotherapy or chemoradiotherapy or are not fit for these treatments, were recruited. These patients were prescribed AP concentrated granules for 4 months. They also received clinical and quality of life assessments for clinical response, as well as positron emission tomography-computed tomography at 3 and 6 months after AP treatment for the assessment of tumor volume. Furthermore, the change in gut microbiota composition after AP treatment was studied. From the results, among the 30 recruited patients, 10 completed the entire course of AP treatment, while 20 received partial AP treatment. Patients who completed the AP treatment achieved significantly longer overall survival periods with the maintenance of the quality of life during the survival period when compared to those who could not complete AP treatment. The treatment effect of AP also contributed to the shift of the overall structure of gut microbiota for ESCC patients towards those of healthy individuals. The significance of this study is the establishment of AP as a safe and effective palliative treatment for patients with squamous cell carcinoma of the esophagus. To the best of our knowledge, this is the first clinical trial of AP water extract in esophageal cancer patients demonstrating its new medicinal use.

Alterations in faecal microbiome and resistome in Chinese international travellers: a metagenomic analysis.

BACKGROUND: International travel increases the risk of acquisition of antibiotic-resistant bacteria and antibiotic resistance genes (ARGs). Previous studies have characterized the changes in the gut microbiome and resistome of Western travellers; however, information on non-Western populations and the effects of travel-related risk factors on the gut microbiome and resistome remains limited. METHODS: We conducted a prospective observational study on a cohort of 90 healthy Chinese adult residents of Hong Kong. We characterized the microbiome and resistome in stools collected from the subjects before and after travelling to diverse international locations using shotgun metagenomic sequencing and examined their associations with travel-related variables. RESULTS: Our results showed that travel neither significantly changed the taxonomic composition of the faecal microbiota nor altered the alpha (Shannon) or beta diversity of the faecal microbiome or resistome. However, travel significantly increased the number of ARGs. Ten ARGs, including aadA, TEM, mgrB, mphA, qnrS9 and tetR, were significantly enriched in relative abundance after travel, eight of which were detected in metagenomic bins belonging to Escherichia/Shigella flexneri in the post-trip samples. In sum, 30 ARGs significantly increased in prevalence after travel, with the largest changes observed in tetD and a few qnrS variants (qnrS9, qnrS and qnrS8). We found that travel to low- or middle-income countries, or Africa or Southeast Asia, increased the number of ARG subtypes, whereas travel to low- or middle-income countries and the use of alcohol-based hand sanitizer (ABHS) or doxycycline as antimalarial prophylaxis during travel resulted in increased changes in the beta diversity of the faecal resistome. CONCLUSIONS: Our study highlights travel to low- or middle-income countries, Africa or Southeast Asia, a long travel duration, or the use of ABHS or doxycycline as antimalarial prophylaxis as important risk factors for the acquisition/enrichment of ARGs during international travel.

Convergent dysbiosis of upper aerodigestive microbiota between patients with esophageal and oral cavity squamous cell carcinoma.

The bidirectional association between primary esophageal squamous cell carcinoma (ESCC) and oral cavity squamous cell carcinoma (OSCC) suggests common risk factors and oncogenic molecular processes but it is unclear whether these two cancers display similar patterns of dysbiosis in their upper aerodigestive microbiota (UADM). We conducted a case-control study to characterize the microbial communities in esophageal lavage samples from 49 ESCC patients and oral rinse samples from 91 OSCC patients using 16S rRNA V3-V4 amplicon sequencing. Compared with their respective non-SCC controls from the same anatomical sites, 32 and 45 discriminative bacterial genera were detected in ESCC and OSCC patients, respectively. Interestingly, 20 of them were commonly enriched or depleted in both types of cancer, suggesting a convergent niche adaptation of upper aerodigestive SCC-associated bacteria that may play important roles in the pathogenesis of malignancies. Notably, Fusobacterium, Selenomonas, Peptoanaerobacter and Peptostreptococcus were enriched in both ESCC and OSCC, whereas Streptococcus and Granulicatelia were commonly depleted. We further identified Fusobacterium nucleatum as the most abundant species enriched in the upper aerodigestive SCC microenvironment, and the higher relative abundances of Selenomonas danae and Treponema maroon were positively correlated with smoking. In addition, predicted functional analysis revealed several depleted (eg, lipoic acid and pyruvate metabolism) and enriched (eg, RNA polymerase and nucleotide excision repair) pathways common to both cancers. Our findings reveal a convergent dysbiosis in the UADM between patients with ESCC and OSCC, suggesting a shared niche adaptation of host-microbiota interactions in the pathogenesis of upper aerodigestive tract malignancies.

Extent of Oral-Gut Transmission of Bacterial and Fungal Microbiota in Healthy Chinese Adults.

Recent studies have provided evidence on the presence of an oral-gut microbiota axis in gastrointestinal diseases; however, whether a similar axis exists in healthy individuals is still in debate. Here, we characterized the bacterial and fungal microbiomes in paired oral rinse and stool samples collected from 470 healthy Chinese adults by sequencing the 16S rRNA V3-V4 and ITS1 regions, respectively. We hypothesized that there is limited oral-gut transmission of both the bacterial and fungal microbiota in healthy Chinese adults. Our results showed that the oral and gut microbiota in healthy individuals differed in taxonomic composition, alpha and beta diversity, metabolic potential, and network properties. Bayesian analysis showed that the vast majority of subjects had negligible or low bacterial and fungal oral-to-stool contribution. Detailed examination of the prevalent amplicon sequence variants (ASVs) also revealed limited cases of sharing between the oral and stool samples within the same individuals, except a few bacterial and fungal ASVs. Association analysis showed that sharing of the potentially transmissible fungal ASVs was associated with host factors, including an older age and a higher body mass index. Our findings indicate that oral-gut transmission of both bacterial and fungal microbiota in healthy adults is limited. Detection of a large amount of shared bacterial or fungal members between the oral and gut microbiome of an individual may indicate medical conditions that warrant detailed checkup. IMPORTANCE The oral-gut microbiota axis in health is a fundamentally important and clinically relevant topic; however, our current understanding of it remains biased and incomplete. By characterizing the bacterial and fungal microbiomes in paired oral rinse and stool samples from a large cohort of healthy Chinese adults, here we provided new evidence that oral-gut microbiota transmission is limited in non-Western population and across biological domains. Our study has established an important baseline of a healthy oral-gut microbiota axis, with which other disease conditions can be compared. Besides, our findings have practical implications that detection of a large amount of shared bacterial or fungal members between the oral cavity and gut within the same individual as an indicator of potential medical conditions.

Characterization of oral microbiota in HPV and non-HPV head and neck squamous cell carcinoma and its association with patient outcomes.

OBJECTIVE: To investigate the interplay among the oral microbiota, HPV infection, traditional risk factors and patient outcomes in head and neck squamous cell carcinoma (HNSCC). MATERIALS AND METHODS: A multi-center study of HNSCC patients with paired tumor and control tissues. We characterized the oral microbiota and HPV infection of tissues in 166 Chinese adults by sequencing the bacterial 16S rRNA V3-V4 and HPV L1 regions, respectively, and examined the associations among the oral microbiota, HPV and clinical features. RESULTS: A total of 15.7% of the surveyed HNSCC patients were positive for HPV DNA, with infection rates varying from 66.7% in oropharyngeal SCC to 10.4% in oral cavity SCC (OSCC). No HPV infection was detected in the surveyed hypopharyngeal SCC. HPV16 was largely the predominant type. HPV infection in non-OSCC, especially oropharyngeal SCC, was associated with advanced N stage and superior survival outcomes. Oral microbiota dysbiosis was observed in HNSCC tumors, with differentially abundant taxa mainly associated with HNSCC subtype, T stage, survival/relapse, HPV infection, and smoking. Notably, the enrichment of Fusobacterium in tumor tissues of OSCC patients was associated with no smoking, early T stage, early N stage, and better 3-year disease-specific survival. CONCLUSION: Our findings underscore the involvement of oral microbiota dysbiosis in OSCC pathogenesis, Fusobacterium is involved with improved OSCC patient outcomes, especially in patients lacking traditional risk factors. Understanding the complex interactions among the oral microbiota, HPV infection and other risk factors for HNSCC will provide important insights into the pathogenesis of HNSCC.

Limited Impact of SARS-CoV-2 on the Human Naso-Oropharyngeal Microbiota in Hospitalized Patients.

Numerous studies have reported dysbiosis in the naso- and/or oro-pharyngeal microbiota of COVID-19 patients compared with healthy individuals; however, only a few small-scale studies have also included a disease control group. In this study, we characterized and compared the bacterial communities of pooled nasopharyngeal and throat swabs from hospitalized COVID-19 patients (n = 76), hospitalized non-COVID-19 patients with respiratory symptoms or related illnesses (n = 69), and local community controls (n = 76) using 16S rRNA gene V3-V4 amplicon sequencing. None of the subjects received antimicrobial therapy within 2 weeks prior to sample collection. Both COVID-19 and non-COVID-19 hospitalized patients differed in the composition, alpha and beta diversity, and metabolic potential of the naso-oropharyngeal microbiota compared with local controls. However, the microbial communities in the two hospitalized patient groups did not differ significantly from each other. Differential abundance analysis revealed the enrichment of nine bacterial genera in the COVID-19 patients compared with local controls; however, six of them were also enriched in the non-COVID-19 patients. Bacterial genera uniquely enriched in the COVID-19 patients included Alloprevotella and Solobacterium. In contrast, Mogibacterium and Lactococcus were dramatically decreased in COVID-19 patients only. Association analysis revealed that Alloprevotella in COVID-19 patients was positively correlated with the level of the inflammation biomarker C-reactive protein. Our findings reveal a limited impact of SARS-CoV-2 on the naso-oropharyngeal microbiota in hospitalized patients and suggest that Alloprevotella and Solobacterium are more specific biomarkers for COVID-19 detection. IMPORTANCE Our results showed that while both COVID-19 and non-COVID-19 hospitalized patients differed in the composition, alpha and beta diversity, and metabolic potential of the naso-oropharyngeal microbiota compared with local controls, the microbial communities in the two hospitalized patient groups did not differ significantly from each other, indicating a limited impact of SARS-CoV-2 on the naso-oropharyngeal microbiota in hospitalized patients. Besides, we identified Alloprevotella and Solobacterium as bacterial genera uniquely enriched in COVID-19 patients, which may serve as more specific biomarkers for COVID-19 detection.

Alterations in gut microbiota of esophageal squamous cell carcinoma patients.

BACKGROUND AND AIM: Esophageal squamous cell carcinoma (ESCC) is the most common histological subtype of esophageal cancer worldwide. Patients with ESCC display an altered esophageal microbiota compared with healthy individuals; however, little is known about the gut microbiota in ESCC. METHODS: Here, we characterized the fecal microbiota of 15 ESCC patients and 16 healthy control subjects using 16S rRNA gene sequencing. RESULTS: After controlling for potential confounders, significant alterations in both taxonomic and functional composition of the gut microbiota in ESCC patients were observed. By contrast, alpha diversity of the gut microbiota did not significantly differ between the cases and controls. We observed an enrichment of potentially pro-inflammatory and/or carcinogenic bacteria, such as Butyricimonas, Veillonella, and Streptococcus, and a depletion of butyrate-producing and/or potentially anti-inflammatory bacteria, such as Butyricicoccus, Lachnospiraceae NK4A136 group, and Eubacterium eligens group, in the gut microbiota of ESCC patients. The log-ratios of Streptococcus to Butyricicoccus and Streptococcus to Lachnospiraceae NK4A136 group of the gut microbiota were identified as potential diagnostic biomarkers for ESCC, with an area under the receiver operating characteristic (ROC) curve (AUC) of 0.863 (95% confidence interval: 0.707-1.000) and 0.825 (0.673-0.977), respectively. The diagnostic performance of both microbial biomarkers was validated in another ESCC cohort. CONCLUSIONS: This pilot study has revealed an altered gut microbiota in ESCC patients and has paved the way for large-scale prospective cohort studies to examine the causative relationship between ESCC and gut dysbiosis.

Anti-inflammatory activities of natural cyclopeptide RA-XII in colitis-associated colon cancer mouse model and its effect on gut microbiome.

Colorectal cancer (CRC), the third most common cancer globally, is associated with intestinal inflammation that leads to poor prognosis. RA-XII, a natural cyclopeptide, has previously been reported to possess anti-tumor activities. Here, the anti-inflammatory activities of RA-XII were investigated in colitis-associated colon cancer mice and a co-culture in vitro model, in which colon cancer cells HCT116 and macrophages RAW264.7 were grown together to mimic the inflammatory microenvironment of CRC. Changes of inflammatory-related molecules and protein expressions in cells were evaluated after RA-XII incubation. Besides, azoxymethane and dextran sulfate sodium-induced colitis-associated colon cancer mice were treated with RA-XII for 24 days, inflammatory parameters and gut microbiome alterations were studied. Our results showed that RA-XII reversed the inflammatory responses of RAW264.7 cells induced by LPS and modulated the protein expressions of AKT, STAT3/p-STAT3, P70S6K, NF-κB and GSK3ß and suppressed the expression of LC3A/B in HCT116 cells in co-culture system. RA-XII treatment restored the colitis damage in colon, reduced colon tumors numbers and decreased inflammatory factors (IL-6, IL-10 and TNF-α). The role of RA-XII on regulating gut microbiome was also demonstrated for the first time. In conclusion, our findings provided new scientific evidence for developing RA-XII as a potent anti-inflammatory agent for CRC.

Determinants and Interactions of Oral Bacterial and Fungal Microbiota in Healthy Chinese Adults.

Numerous studies have examined the composition of and factors shaping the oral bacterial microbiota in healthy adults; however, similar studies on the less dominant yet ecologically and clinically important fungal microbiota are scarce. In this study, we characterized simultaneously the oral bacterial and fungal microbiomes in a large cohort of systemically healthy Chinese adults by sequencing the bacterial 16S rRNA gene and fungal internal transcribed spacer. We showed that different factors shaped the oral bacterial and fungal microbiomes in healthy adults. Sex and age were associated with the alpha diversity of the healthy oral bacterial microbiome but not that of the fungal microbiome. Age was also a major factor affecting the beta diversity of the oral bacterial microbiome; however, it only exerted a small effect on the oral fungal microbiome when compared with other variables. After controlling for age and sex, the bacterial microbiota structure was most affected by marital status, recent oral conditions and oral hygiene-related factors, whereas the fungal microbiota structure was most affected by education level, fruits and vegetables, and bleeding gums. Bacterial-fungal interactions were limited in the healthy oral microbiota, with the strongest association existing between Pseudomonas sp. and Rhodotorula dairenensis. Several bacterial amplicon sequence variants (ASVs) belonging to Veillonella atypica and the genera Leptotrichia, Streptococcus and Prevotella_7 and fungal ASVs belonging to Candida albicans and the genus Blumeria were revealed as putative pivotal members of the healthy oral microbiota. Overall, our study has facilitated understanding of the determining factors and cross-kingdom interactions of the healthy human oral microbiome. IMPORTANCE Numerous studies have examined the bacterial community residing in our oral cavity; however, information on the less dominant yet ecologically and clinically important fungal members is limited. In this study, we characterized simultaneously the oral bacterial and fungal microbial communities in a large cohort of healthy Chinese adults, examined their associations with an array of host factors, and explored potential interactions between the two microbial groups. We showed that different factors shape the diversity and structure of the oral bacterial and fungal microbial communities in healthy adults, with, for instance, sex and age only associated with the diversity of the bacterial community but not that of the fungal community. Besides, we found that bacterial-fungal interactions are limited in the healthy oral cavity. Overall, our study has facilitated understanding of the determining factors and bacterial-fungal interactions of the healthy human oral microbial community.

Network pharmacology reveals potential functional components and underlying molecular mechanisms of Andrographis paniculata in esophageal cancer treatment.

Antitumor and antimetastatic effects of the medicinal herb Andrographis paniculata (AP) in esophageal cancer (EC) have been previously reported. In this study, we aimed to uncover the potential functional components and the underlying molecular mechanisms of AP in EC treatment using network pharmacology and experimental validation. Twenty-two potential active AP compounds against EC were revealed, including the antitumor/antiinflammatory compounds panicolin, moslosooflavone, and deoxyandrographiside. Epidermal growth factor receptor (EGFR), signal transducer and activator of transcription 3 (STAT3), RAC-alpha serine/threonine-protein kinase (AKT1), prostaglandin-endoperoxide synthase 2 (PTGS2), chemokine (C-X-C motif) ligand 8 (CXCL8), phosphatidylinositol 4,5-bisphosphate 3-kinase subunit alpha (PIK3CA), and toll-like receptor 4 (TLR4) were most highly ranked among the predicted targets of AP in EC treatment and may play important roles in the anti-EC effects of AP. KEGG pathway analysis revealed the enrichment of multiple cancer-related pathways and signaling pathways. Quantitative reverse transcription-polymerase chain reaction (qRT-PCR) and western blotting validation showed that overnight treatment with 850.3 µg/ml of AP water extract significantly reduced the mRNA expressions of EGFR and AKT in human EC-109 cells. The presence of panicolin and moslosooflavone in the AP water extract samples were confirmed using LC-MS against reference standards. This study has comprehensively revealed for the first time the potential functional components of AP in EC and explored the underlying molecular mechanisms. Future studies should characterize the potential pharmacological properties of the other highly ranked yet understudied compounds in AP detected.

Integrated Network Pharmacology Analysis and In Vitro Validation Revealed the Potential Active Components and Underlying Mechanistic Pathways of Herba Patriniae in Colorectal Cancer.

Herba Patriniae (HP) are medicinal plants commonly used in colorectal cancer (CRC) patients. In this study, network pharmacology was used to predict the active components and key signaling pathways of HP in CRC. Patrinia heterophylla, one type of HP, was chosen for validation of the network pharmacology analysis. The phytochemical profile of Patrinia heterophylla water extract (PHW) was determined by UHPLC-MS. MTT, RT-PCR, and Western blot assays were performed to evaluate the bioactivities of PHW in colon cancer cells. Results showed that 15 potentially active components of HP interacted with 28 putative targets of CRC in the compound-target network, of which asperglaucide had the highest degree. Furthermore, the ErbB signaling pathway was identified as the pathway mediated by HP with the most potential against CRC. Both RT-PCR and Western blot results showed that PHW significantly downregulated the mRNA and protein levels of EGFR, PI3K, and AKT in HCT116 cells. Asperglaucide, present in PHW, exhibited an anti-migratory effect in HCT116 cells, suggesting that it could be an active component of PHW in CRC treatment. In conclusion, this study has provided the first scientific evidence to support the use of PHW in CRC and paved the way for further research into the underlying mechanisms of PHW against CRC.

RNA-Seq-based high-resolution linkage map reveals the genetic architecture of fruiting body development in shiitake mushroom, Lentinula edodes.

Fruiting body development (FBD) of mushroom-forming fungi has attracted tremendous interest. However, the genetic and molecular basis of FBD is poorly known. Here, using Lentinula edodes (shiitake) as a model, we deciphered the genetic architecture underlying fruiting body-related traits (FBRTs) by combined genomic, genetic and phenotypic data. Using RNA-Seq of fruiting bodies from 110 dikaryons in a bi-parental mapping population, we constructed an ultra-high-density genetic map of L. edodes (Lemap2.0) with a total length of 810.14 cM, which covered 81.7% of the shiitake genome. A total of 94 scaffolds of the shiitake genome were aligned to Lemap2.0 and re-anchored into nine pseudo-chromosomes. Then via quantitative trait locus (QTL) analysis, we disclosed an outline of the genetic architecture of FBD in shiitake. Twenty-nine QTLs and three main genomic regions associated with FBD of shiitake were identified. Using meta-QTL analysis, seven pleiotropic QTLs for multiple traits were detected, which contributed to the correlations of FBRTs. In the mapped QTLs, the expression of 246 genes were found to significantly correlate with the phenotypic traits. Thirty-three of them were involved in FBD and could represent candidate genes controlling the shape and size of fruiting bodies. Collectively, our findings have advanced our understanding of the genetic regulation of FBD in shiitake and mushroom-forming fungi at large.

Gut Microbiota in Decapod Shrimps: Evidence of Phylosymbiosis.

Gut microbiota have long attracted the interest of scientists due to their profound impact on the well-being of animals. A non-random pattern of microbial assembly that results in a parallelism between host phylogeny and microbial similarity is described as phylosymbiosis. Phylosymbiosis has been consistently observed in different clades of animal hosts, but there have been no studies on crustaceans. In this study, we investigated whether host phylogeny has an impact on the gut microbiota assemblages in decapod shrimps. We examined the gut microbial communities in 20 shrimp species from three families inhabiting distinct environments, using metabarcoding analyses of the V1-V3 hypervariable region of the 16S rRNA gene. Gut microbial communities varied within each shrimp group but were generally dominated by Proteobacteria. A prevalent phylosymbiotic pattern in shrimps was evidenced for the first time by the observations of (1) the distinguishability of microbial communities among species within each group, (2) a significantly lower intraspecific than interspecific gut microbial beta diversity across shrimp groups, (3) topological congruence between host phylogenetic trees and gut microbiota dendrograms, and (4) a correlation between host genetic distances and microbial dissimilarities. Consistent signals of phylosymbiosis were observed across all groups in dendrograms based on the unweighted UniFrac distances at 99% operational taxonomic units (OTUs) level and in Mantel tests based on the weighted UniFrac distances based on 97% OTUs and amplicon sequence variants. Penaeids exhibited phylosymbiosis in most tests, while phylosymbiotic signals in atyids and pandalids were only detected in fewer than half of the tests. A weak phylogenetic signal was detected in the predicted functions of the penaeid gut microbiota. However, the functional diversities of the two caridean groups were not significantly related to host phylogeny. Our observations of a parallelism in the taxonomy of the gut microbiota with host phylogeny for all shrimp groups examined and in the predicted functions for the penaeid shrimps indicate a tight host-microbial relationship during evolution.

A preliminary examination of the bacterial, archaeal, and fungal rhizosphere microbiome in healthy and Phellinus noxius-infected trees.

Phellinus noxius is a pathogenic fungus that causes brown root rot disease, resulting in a widespread tree and crop mortality in the tropics and subtropics. Early stages of this disease are largely asymptomatic, hindering early diagnosis and effective treatment. We hypothesized that P. noxius infection would alter the rhizosphere microbiome of infected trees, based on which diagnostic biomarkers could be developed. Here, we examined for the first time the bacterial, archaeal, and fungal rhizosphere microbiome in four species of healthy and P. noxius-infected trees (Ficus microcarpa, Celtis sinensis, Mallotus paniculatus, and Cinnamomum camphora) using high-throughput amplicon sequencing. Results revealed the dominance of Proteobacteria and Actinobacteria in bacteria, Crenarchaeota and Euryarchaeota in archaea, and Ascomycota and Basidiomycota in fungi. Phellinus noxius infection did not affect the alpha diversity of the bacterial rhizosphere microbiome in all four tree species but affected that of archaea and fungi in a tree species-dependent manner. Infection with P. noxius only affected the bacterial rhizosphere composition in M. paniculatus but not the other three tree species. By contrast, P. noxius infection affected the composition of the archaeal and fungal rhizosphere microbiome in all four tree species. Collectively, these results suggest that potential diagnostic biomarkers for brown root rot disease are tree species-specific and should be developed based on different taxonomic groups. Our study has provided insights into the rhizosphere microbiome in healthy and P. noxius-infected trees and laid a solid foundation for future comprehensive studies.

Discovery of an interplay between the gut microbiota and esophageal squamous cell carcinoma in mice.

Esophageal squamous cell carcinoma (ESCC) is the main type of esophageal cancer (EC) worldwide, causing half a million deaths each year. Recent evidence has demonstrated the role of the gut microbiota in health and disease. However, our current understanding of the gut microbiome in EC remains scarce. Here, we characterized the gut and esophageal microbiome in a metastatic mouse model of ESCC and examined the functional roles of the gut microbiota in EC development in fecal microbiota transplantation (FMT) experiments. Nude mice intraperitoneally xenografted with human EC-109 cells showed significant alterations in the overall structure, but not alpha diversity, of the gut and esophageal microbiome as compared to naïve control mice. Xenograft of EC cells depleted the order Pasteurellales in the gut microbiome, and enriched multiple predicted metabolic pathways, including those involved in carbohydrate and lipid metabolism, in the esophageal microbiome. FMT of stool from healthy mice to antibiotic-treated xenograft-bearing mice significantly attenuated liver metastasis, suggesting a protective role of the commensal gut microbiota in EC. Moreover, we showed that combination chemotherapy with cisplatin and 5-fluorouracil, and the anti-EC medicinal herb Andrographis paniculata (AP) differentially affected the gut and esophageal microbiome in EC. FMT experiment revealed a reduced anti-metastatic efficacy of AP on liver metastasis in antibiotic-treated xenograft-bearing mice, suggesting a role of the commensal gut microbiota in the anti-metastatic efficacy of the herb. In conclusion, our findings reveal for the first time an interplay between the gut microbiota and EC and provide insights into the treatment strategies for EC.

A Review of the Effects of Natural Compounds, Medicinal Plants, and Mushrooms on the Gut Microbiota in Colitis and Cancer.

The human gastrointestinal tract harbors a diverse array of microorganisms that play fundamental roles in health and disease. Imbalance in the gut microbiota, namely dysbiosis, can lead to various diseases, including cancer and gastrointestinal tract disorders. Approaches to improve gut dysbiosis, such as dietary intervention, intake of probiotics, and fecal microbiota transplantation are emerging strategies to treat these diseases. Various medicinal botanicals have reported anti-cancer and/or anti-inflammatory properties. Preclinical studies have illustrated that some of these natural products are also capable to modulate the gut microbiota, suggesting their use as possible alternative approach to improve gut dysbiosis and thereby assist diseases treatment. In this review article, we have summarized the current knowledge on the effects of natural compounds, medicinal plants, and mushrooms on the gut microbiota in various cancers and colitis in preclinical animal models. Challenges towards the clinical use of these medicinal botanicals as modulators of the gut microbiota in cancer and colitis treatment are also discussed.

Genome-wide mRNA and miRNA analysis in the early stages of germ tube outgrowth in Coprinopsis cinerea.

Coprinopsis cinerea is a model mushroom-forming basidiomycete which produces basidiospores during sexual reproduction. This fungus is widely used to study fruiting body formation and development. Molecular mechanisms controlling its growth from vegetative mycelium to multicellular mature fruiting body have been studied extensively. However, little is known about the underlying biological processes during germ tube outgrowth or the transition from basidiospores to multinucleate hyphae. To better understand sexual spore germination in fungi, here we examined the time-dependent cellular events at resting, germinating and fully germinated basidiospores of C. cinerea by genome-wide transcriptional and post-transcriptional analyses and by carbohydrate composition analysis. Our results revealed a high demand of protein degradation, and biosynthesis of various compounds at the early stage of basidiospore gemination and dynamic changes of carbohydrate metabolism throughout the germination process. Seven microRNA-like RNAs (milRNAs) were identified in the resting basidiospores of C. cinerea, six of which were basidiospore-specific. Glycogen and trehalose were shown to be the carbon sources supporting the initiation of germ tube outgrowth. One basidiospore-specific milRNA, cci-milR-37, was found to be a potential regulator of glycogen metabolic pathways related to vegetative hyphal growth. Our results demonstrated the mRNA and miRNA-mediated regulation on energy production, protein and carbohydrate metabolisms at the early developmental stages of germ tube to form totipotent hyphae. To our knowledge, this is the first study to show the roles of miRNAs in mushroom basidiospore germination and out-growth.