Sizhe Chen

Dr. Sizhe Chen

orcid

Research Focus & Metrics

Academic Career Length

3Years (2024-Present)

(Calculated once Scilit publication data is synced: current year − year of first publication + 1)

Representative Publications

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10 July 2025 in Life
Verified
Journal Article
Open access
PDF file
YWYun Wang
Yun Wang
SXSuyi Xie
Suyi Xie
SCSizhe Chen
Sizhe Chen
CLChenyu Li
Chenyu Li
YCYeuk Lam Ashley Chan
Yeuk Lam Ashley Chan
SNSiew C Ng
Siew C Ng
Background: Insomnia is one of the most prevalent health concerns and has a major impact on human health and quality of life. Increasing evidence indicates the gut microbiota’s role in sleep regulation through the gut–brain axis. This systematic review aims to summarise current evidence on the role of gut microbiota alterations in insomnia. Methods: We searched PubMed, Embase, and Cochrane Library through November 2024 for case–control studies comparing gut microbiota in insomnia subjects and controls. The primary outcome was changes in microbiota diversity and bacteria taxonomy. Results: We included 15 case–control studies from 14 articles, consisting of 1321 subjects (603 insomnia; 718 controls). Eight studies showed reduced alpha diversity and eleven showed altered beta diversity in insomnia subjects. Depletions of specific taxa such as Lactobacillales (class Bacilli), Faecalibacterium, and Lachnospira and the enrichment of Actinobacteria, Bacteroidales (class Bacteroidia), and several genera, including Streptococcus, Blautia, Lactobacillus, Clostridium, Holdemanella, and Eubacterium hallii, were observed in insomnia subjects. There was a negative association between insomnia severity and abundance of Faecalibacterium and Lachnospira, and positive associations with Blautia. Conclusions: This systematic review identifies specific alterations in gut microbiota among insomnia subjects characterised by taxonomic changes that may serve as promising therapeutic targets for sleep disorders.

31 December 2025 in Nature Communications
Verified
Journal Article
Open access
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YWYuqi Wu
Yuqi Wu
OWOscar Wing Ho Wong
Oscar Wing Ho Wong
SCSizhe Chen
Sizhe Chen
YWYun Wang
Yun Wang
WLWenqi Lu
Wenqi Lu
SNSiew C Ng
Siew C Ng
Autism spectrum disorder (ASD) is linked to both altered gut microbiota and unhealthy diets; however, the mechanistic connections remain elusive. In this study, we conducted a systematic analysis of fecal microbiome metagenomic data, paired with granular dietary assessments and phenotypic profiles, across a cohort of 818 children (462 with ASD, 356 without ASD; mean age = 8.4 years; 27.3% female). By integrating dietary indices, nutrient intake, and food additive exposures, we uncovered ASD-specific linkages to the microbiome. Poor dietary quality correlated with aggregated core autistic symptoms, gastrointestinal complications, and atypical eating behaviors. Notably, children with ASD exhibited a more pronounced diet-microbiome interaction network compared to neurotypical peers, suggesting heightened microbial sensitivity to nutritional inputs. Furthermore, synthetic emulsifiers—specifically polysorbate-80 and carrageenan—were associated with disrupted microbial connectivity in ASD, a phenomenon attenuated in neurotypical children. Our findings elucidate the mechanistic links between dietary factors—particularly synthetic food additives—and microbiome dysregulation in ASD, urging a re-evaluation of dietary guidelines for ASD populations and laying the groundwork for personalized nutritional strategies.

Verified
Journal Article
Open access
PDF file
CLChenyu Li
Chenyu Li
SCSizhe Chen
Sizhe Chen
YWYun Wang
Yun Wang
Qi SUQi SU
Qi SU
Insomnia poses considerable risks to both physical and mental health, leading to cognitive impairment, weakened immune function, metabolic dysfunction, cardiovascular issues, and reduced quality of life. Given the significant global increase in insomnia and the growing scientific evidence connecting gut microbiota to this disorder, targeting gut microbiota as an intervention for insomnia has gained popularity. In this review, we summarize current microbiome-based therapeutics for insomnia, including dietary modifications; probiotic, prebiotic, postbiotic, and synbiotic interventions; and fecal microbiota transplantation. Moreover, we assess the capabilities and weaknesses of these technologies to offer valuable insights for future studies.

14 January 2026 in Nature Communications
Verified
Journal Article
Open access
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SCSizhe Chen
Sizhe Chen
YYYue Yuan
Yue Yuan
YWYun Wang
Yun Wang
YPYe Peng
Ye Peng
Hein M. TunHein M. Tun
Hein M. Tun
Qi SUQi SU
Qi SU
Fecal coprolites preserve ancient microbiomes and are a potential source of extinct but highly efficacious antimicrobial peptides (AMPs). Here, we develop AMPLiT (AMP Lightweight Identification Tool), an efficient tool deployable to portable hardware for AMP screening in metagenomic datasets. AMPLiT demonstrates AUPRC performances of 0.9486 ± 0.0003 and reasonable overall training time of 3200 ± 53 s. By computationally utilizing AMPLiT, we analyze seven ancient human coprolite metagenomes, identifying 160 AMP candidates. Of 40 representative peptides synthesized, 36 (90%) peptides demonstrate measurable antimicrobial activity at 100 μM or less in vitro. Strikingly, approximately two-thirds of these peptides are sourced from Segatella copri , a dominant ancient gut commensal that is conspicuously underrepresented in modern populations, particularly those with Westernized lifestyles. Representative S. copri -derived AMPs exhibit disruptions against membranes of pathogenic bacteria, coupled with low cytotoxicity and hemolytic risk. In vivo, lead peptides demonstrate potent antibacterial and wound-healing efficacy comparable to traditional antibiotics, especially in combating gram-positive pathogens. Our findings highlight the ancient gut microbiomes as sources of novel AMPs, offering valuable insights into the historical role of S. copri in human health and its decline in contemporary populations.

26 February 2026 in Nature Communications
Verified
Journal Article
Open access
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WLWenqi Lu
Wenqi Lu
OWOscar Wing Ho Wong
Oscar Wing Ho Wong
JZJie Zhu
Jie Zhu
SCSizhe Chen
Sizhe Chen
Hein M. TunHein M. Tun
Hein M. Tun
SNSiew C Ng
Siew C Ng
Autism spectrum disorder (ASD) is associated with alteration of gut microbiome, but the influence of familial structure on it remains poorly understood. We investigate gut microbiota across 429 children from multiplex families with multiple affected children, simplex families with one affected child, and single-child ASD families, alongside typically developing controls. We found that children from multiplex families exhibit the most distinct microbiome compositions. Cohabiting siblings in ASD families display higher microbiome similarity than those in healthy families, with a clear gradient in strain-sharing rates that is highest in multiplex, intermediate in simplex, and lowest in healthy siblings. This increased sharing involves specific taxa with reported opportunistic pathogenic potential, such as Eubacterium rectale , alongside reduced sharing of the commensal bacterium Bacteroides xylanisolvens . This suggests that their gut microbiome configurations, which are potentially influenced by shared environmental and host factors, are associated with increased persistence or detectability of specific bacterial strains. Our results underscore the significant contribution of family type to microbial heterogeneity in ASD and provide a hypothesis-generating context for future studies to explore the role of the shared microbial environment in a familial context.

Verified
Journal Article
Open access
PDF file
YWYuqi Wu
Yuqi Wu
OWOscar Wing Ho Wong
Oscar Wing Ho Wong
SCSizhe Chen
Sizhe Chen
YWYun Wang
Yun Wang
GZguoqing Zhang
guoqing Zhang
Qi SUQi SU
Qi SU
Autism spectrum disorder (ASD) frequently co-occurs with malnutrition and gut dysbiosis, yet the underlying mechanisms remain poorly understood. Herein, this cross-sectional study first profiles dietary intake differences using dietary records from 210,874 participants (ASD = 232; non-ASD = 210,642; median age = 56.18) from the UK Biobank (UKB). Second, a bi-directional Mendelian Randomization (MR) approach serves to dissect relationships between ASD genetic susceptibility and dietary preferences by leveraging genome-wide association metadata from the iPSYCH-PGC (ASD) and UKB (dietary intake/food-liking traits). The same strategy is implemented to identify ASD-associated gut microbial species. Mediation analyses further assess the role of gut microbiota in the association between ASD and dietary preferences. Subjects with ASD exhibit higher consumption of cheese, processed meat, and oily fish, alongside lower intake of fruits, and demonstrate a preference for high-fat/salt and energy-dense foods. Additionally, the depletion of Turicibacter, Streptococcus, and Lachnospiraceae NK4A136 was causally related with ASD (all false discovery rate < 0.05; β = −0.15, β = −0.10, β = −0.093, respectively), which significantly mediates the ASD-associated elevated preference for high-fat/salt foods. In conclusion, ASD is associated with specific dietary preferences, likely mediated via gut microbiota, highlighting the future potential of gut microbiome-based therapeutics to modify eating disorders for ASD.