Man Kit Cheung

Peatlands are vital long-term carbon sinks but can also be greenhouse gas sources, with the balance largely governed by microbial processes. However, the structure and function of peatland microbial communities are currently poorly characterised at the global scale, limiting our understanding of their response to climate change. Here, we present a global analysis of the peatland microbiome by leveraging a dataset of 109 publicly available metagenomes from 20 near-natural peatland sites worldwide. We identify dominant vegetation and peatland type as the strongest predictors of peatland microbiome taxonomy and function. Different peatland types host distinct microbiomes, with implications for the main microbial processes in these ecosystems. We reveal a high metabolic potential of the northern bog microbiome for plant organic matter degradation, largely attributed to Acidobacteriota. Moreover, we show that the tropical peatland microbiome exhibits a broad metabolic potential for key peatland biogeochemical processes, including methanogenesis and denitrification, across all depths. Intriguingly, we observe an impaired potential for complete denitrification in a significant proportion of the northern fen metagenomes, providing implications for nitrous oxide emissions as a greenhouse gas. Overall, our study provides key insights into the global patterns and ecological drivers of the peatland microbiome, enhancing our understanding of their response to climate change.

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/β-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.

The first few years of life is a key period for the development of the gut microbiome. However, our current understanding of this topic is largely biased toward Western populations. In this study, we characterized the development and determinants of the gut microbiome in a prospective cohort of 112 term Chinese children by sequencing 713 stool samples collected at nine time points from birth to 3 years of age using 16S rRNA gene sequencing. We revealed alterations in the composition and alpha and beta diversities of the gut microbiota across the first 3 years of life. We identified mode of delivery, feeding mode, and intrapartum antibiotics as the major determinants of the early-life gut microbiome, the effects of all of which persisted up to 12 months. Importantly, by conducting a nested case–control study, we showed that alterations in the infant gut microbiota precede the development of eczema. Interestingly, we identified a depletion of Bacteroides and an enrichment of Clostridium sensu stricto 1 in the gut microbiome of infants with eczema at 1 year old. The same patterns were also observed in C-section-born infants within the same time frames, suggesting a role of the gut microbiota in previously reported associations between C-section and increased risk of eczema. Our study has revealed important associations between the gut microbiome and eczema in infancy and has established the basis for potential prevention/treatment of eczema via modulation of the gut microbiota. 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.

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 remain limited. 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. 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. Thirty 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. 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.

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.

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 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.

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.

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.

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.