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Cells
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The Multifaceted Microbiome in Health and Disease
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The Multifaceted Microbiome in Health and Disease

A special issue of Cells (ISSN 2073-4409).

Deadline for manuscript submissions: closed (15 May 2023) | Viewed by 20584

Special Issue Editor

Dr. Jessie Qiaoyi Liang

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Guest Editor
Department of Medicine and Therapeutics, Centre for Gut Microbiota Research, Faculty of Medicine, Li Ka Shing Institute of Health Science, CUHK Shenzhen Research Institute, The Chinese University of Hong Kong, Hong Kong, China
Interests: microbiome in health and disease; human endogenous retroviruses; cancer genomics and epigenetics; biomarkers and molecular diagnostics
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

There are trillions of microorganisms—bacteria, fungi, protozoa, and viruses—living upon and within the human body, outnumbering the human cells by at least 10 to 1. These microbes contain 3.3 million genes, dwarfing the human genome's 23,000. The human microbiome refers to the genome of all the microbes. It is now well accepted that the microbes in the human body play a considerable role in health and diseases. New evidence is emerging that the dysbiotic microbiome influences the development of diseases in various organs, including the intestine, skin, respiratory tract, neural system, and others. The dysbiotic microbiome has direct and indirect effects on disease progression through a decrease in beneficial microbes and increases in pathogenic ones. The microbiome plays roles in many aspects, from producing metabolites that impact disease progression, to influencing the efficacy of treatments.

In addition to etiology study, microbiome research has advanced to other levels, including disease diagnosis, prevention, intervention, treatment by fecal microbiota transplantation, and adjuvant treatment during chemotherapy or immunotherapy. In this regard, ethical issues have emerged surrounding the application or manipulation of the human microbiome for diagnosis, prevention, intervention, and treatment.

In this Special Issue, we would like to shed light on the roles of microbiome in health and diseases of various organs, and research on microbiome at different levels including etiology, diagnosis, prevention, intervention, treatment, and the related ethical issues. We welcome original research articles and state-of-the-art reviews on any aspects of microbiome in health and diseases.

Dr. Jessie Qiaoyi Liang
Guest Editor

Manuscript Submission Information

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Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Cells is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2700 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • microbiome
  • dysbiosis
  • asthma
  • inflammatory bowel diseases
  • Clostridioides difficile
  • antibiotic resistance
  • microbiome-based intervention
  • host-microbiome interactions

Published Papers (6 papers)

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Research

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12 pages, 1795 KiB  
Article
A Probiotic Formula for Modulation of Colorectal Cancer Risk via Reducing CRC-Associated Bacteria
by Jessie Qiaoyi Liang, Yao Zeng, Effie Yin Tung Lau, Yuting Sun, Yao Huang, Tingyu Zhou, Zhilu Xu, Jun Yu, Siew Chien Ng and Francis Ka Leung Chan
Cells 2023, 12(9), 1244; https://0-doi-org.brum.beds.ac.uk/10.3390/cells12091244 - 25 Apr 2023
Cited by 6 | Viewed by 2193
Abstract
Gut microbiota dysbiosis with increased pathogenic bacteria and decreased beneficial bacteria is associated with colorectal cancer (CRC) development. This study examined the effect of a newly developed probiotic formula in modulating CRC-related bacteria. We developed a probiotic formula containing three bifidobacteria (B. [...] Read more.
Gut microbiota dysbiosis with increased pathogenic bacteria and decreased beneficial bacteria is associated with colorectal cancer (CRC) development. This study examined the effect of a newly developed probiotic formula in modulating CRC-related bacteria. We developed a probiotic formula containing three bifidobacteria (B. adolescentis, B. longum, and B. bifidum) based on the identification of bacterial species that showed significant correlations with CRC-related bacteria including Fusobacterium nucleatum (Fn), Lachnoclostridium sp. m3, Clostridium hathewayi (Ch), and Bacteroides clarus (Bc). We co-cultured Fn with each bifidobacterium or the combined formula and examined the growth of Fn by qPCR. The three individual bifidobacteria significantly inhibited the growth of Fn compared to the control treatment (24~65% inhibition; all p < 0.001). The combination of the three bifidobacteria showed a greater inhibitory effect on Fn growth (70% inhibition) than the individual bifidobacteria (all p < 0.05). We further examined the effect of the probiotic formula in a pilot study of 72 subjects (40 on probiotics; 32 with no intervention) for 4 weeks and followed them up for 12 weeks. The relative fecal abundances of the bifidobacteria in the formula and the CRC-related markers (Fn, m3, Ch, and Bc) were quantitated by qPCR before and after the intervention, and the combined CRC risk score (4Bac; Fn, m3, Ch, and Bc) was evaluated. Subjects with probiotics intervention showed significantly increased abundances of the bifidobacteria from week 2 to week 5 compared to baseline (p < 0.05), and the abundances dropped to baseline levels after the cessation of the intervention. There were significant decreases in the levels of CRC-related markers (Fn and m3) and the CRC risk score (4Bac) from week 2 to week 12 compared to baseline levels (p < 0.05) in the intervention group but not in the control group. A novel probiotic formula containing B. adolescentis, B. longum, and B. bifidum was effective in inhibiting the growth of F. nucleatum in vitro and improving the gut microbial environment against CRC development. Full article
(This article belongs to the Special Issue The Multifaceted Microbiome in Health and Disease)
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20 pages, 4390 KiB  
Article
Changes in Gut Microbiota and Systemic Inflammation after Synbiotic Supplementation in Patients with Systemic Lupus Erythematosus: A Randomized, Double-Blind, Placebo-Controlled Trial
by Alvina Widhani, Samsuridjal Djauzi, Franciscus Dhyanagiri Suyatna and Beti Ernawati Dewi
Cells 2022, 11(21), 3419; https://0-doi-org.brum.beds.ac.uk/10.3390/cells11213419 - 29 Oct 2022
Cited by 16 | Viewed by 3727
Abstract
Gut dysbiosis has a role in the pathogenesis of lupus. Synbiotic supplementation may restore the balance of gut microbiota. This study investigated whether synbiotics could improve gut microbiota and systemic inflammation in lupus patients. This randomized, double-blind, placebo-controlled trial was conducted in adult [...] Read more.
Gut dysbiosis has a role in the pathogenesis of lupus. Synbiotic supplementation may restore the balance of gut microbiota. This study investigated whether synbiotics could improve gut microbiota and systemic inflammation in lupus patients. This randomized, double-blind, placebo-controlled trial was conducted in adult systemic lupus erythematosus (SLE) patients. Subjects were randomized to receive either synbiotics or a placebo. Fecal microbiota, hs-CRP, IL-6, and IL-17 were measured at baseline and after 60 days. Patients who fulfilled the inclusion criteria were randomized into synbiotic (n = 23) and placebo groups (n = 23). In the synbiotic group, hs-CRP was not significantly increased (1.8 [0.9; 4.85] vs. 2.1 [0.9; 4.25] mg/L; pre vs. post; p = 0.23), whereas in the placebo group hs-CRP was increased significantly (1.75 [0.4; 4.45] vs. 3.75 [0.58; 7.05] mg/L; pre vs. post; p = 0.005). In the synbiotic group, IL-6 decreased significantly (8.76 [6.62; 11.39] vs. 6.59 [4.96; 8.01]; pre vs. post; p = 0.02), while there was no significant change in IL-17 level. In the placebo group, there was no significant change in IL-6 and IL-17. Synbiotic supplementation increased the Firmicutes:Bacteroidetes ratio (0.05 ± 0.60 vs. −0.08 ± 0.63, synbiotic vs. placebo p = 0.48) and butyrate metabolism (p = 0.037) and decreased amino sugar and nucleotide sugar metabolism (p = 0.040). There was improvement in the SLE disease activity index 2K (SLEDAI-2K) score in the synbiotic group (14 [9; 16] vs. 8 [2; 12]; pre vs. post; p < 0.001), while no change in the placebo group (9 [8; 18.25] vs. 9 [5.5; 15]; pre vs. post; p = 0.31). Synbiotic supplementation could reduce systemic inflammation and SLE disease activity and alter the composition and functions of gut microbiota. Full article
(This article belongs to the Special Issue The Multifaceted Microbiome in Health and Disease)
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16 pages, 2283 KiB  
Article
Endogenous Ethanol and Triglyceride Production by Gut Pichia kudriavzevii, Candida albicans and Candida glabrata Yeasts in Non-Alcoholic Steatohepatitis
by Babacar Mbaye, Patrick Borentain, Reham Magdy Wasfy, Maryam Tidjani Alou, Nicholas Armstrong, Giovanna Mottola, Line Meddeb, Stéphane Ranque, René Gérolami, Matthieu Million and Didier Raoult
Cells 2022, 11(21), 3390; https://0-doi-org.brum.beds.ac.uk/10.3390/cells11213390 - 27 Oct 2022
Cited by 20 | Viewed by 3171
Abstract
Nonalcoholic steatohepatitis (NASH) increases with fructose consumption and metabolic syndrome and has been recently linked with endogenous ethanol production, notably by high alcohol-producing Klebsiella pneumoniae (HiAlc Kpn). Candida yeasts are the main causes of auto-brewery syndromes but have been neglected in NASH. Here, [...] Read more.
Nonalcoholic steatohepatitis (NASH) increases with fructose consumption and metabolic syndrome and has been recently linked with endogenous ethanol production, notably by high alcohol-producing Klebsiella pneumoniae (HiAlc Kpn). Candida yeasts are the main causes of auto-brewery syndromes but have been neglected in NASH. Here, the fecal ethanol and microbial content of 10 cases and 10 controls were compared. Ethanol was measured by gas chromatography-mass spectrometry. Species identification was performed by MALDI-TOF MS, and triglyceride production was assessed by a colorimetric enzymatic assay. The fecal ethanol concentration was four times higher in patients with NASH (median [interquartile range]: 0.13 [0.05–1.43] vs. 0.034 [0.008–0.57], p = 0.037). Yeasts were isolated from almost all cases but not from controls (9/10 vs. 0/10, p = 0.0001). Pichia kudriavzevii was the most frequent (four patients), while Candida glabrata, Candida albicans, and Galactomyces geotrichum were identified in two cases each. The concentration of ethanol produced by yeasts was 10 times higher than that produced by bacteria (median, 3.36 [0.49–5.60] vs. 0.32 [0.009–0.43], p = 0.0029). Using a 10% D-fructose restricted medium, we showed that NASH-associated yeasts transformed fructose in ethanol. Unexpectedly, yeasts isolated from NASH patients produced a substantial amount of triglycerides. Pichia kudriavzevii strains produced the maximal ethanol and triglyceride levels in vitro. Our preliminary human descriptive and in vitro experimental results suggest that yeasts have been neglected. In addition to K. pneumoniae, gut Pichia and Candida yeasts could be linked with NASH pathophysiology in a species- and strain-specific manner through fructose-dependent endogenous alcohol and triglyceride production. Full article
(This article belongs to the Special Issue The Multifaceted Microbiome in Health and Disease)
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19 pages, 4266 KiB  
Article
Akkermansia muciniphila Reduces Peritonitis and Improves Intestinal Tissue Wound Healing after a Colonic Transmural Defect by a MyD88-Dependent Mechanism
by Radu Bachmann, Matthias Van Hul, Pamela Baldin, Daniel Léonard, Nathalie M. Delzenne, Clara Belzer, Janneke P. Ouwerkerk, Dirk Repsilber, Ignacio Rangel, Alex Kartheuser, Robert Jan Brummer, Willem M. De Vos and Patrice D. Cani
Cells 2022, 11(17), 2666; https://0-doi-org.brum.beds.ac.uk/10.3390/cells11172666 - 27 Aug 2022
Cited by 9 | Viewed by 3625
Abstract
Anastomotic leakage is a major complication following colorectal surgery leading to peritonitis, complications, and mortality. Akkermansia muciniphila has shown beneficial effects on the gut barrier function. Whether A. muciniphila reduces peritonitis and mortality during colonic leakage is unknown. Whether A. muciniphila can directly [...] Read more.
Anastomotic leakage is a major complication following colorectal surgery leading to peritonitis, complications, and mortality. Akkermansia muciniphila has shown beneficial effects on the gut barrier function. Whether A. muciniphila reduces peritonitis and mortality during colonic leakage is unknown. Whether A. muciniphila can directly modulate the expression of genes in the colonic mucosa in humans has never been studied. We investigated the effects of a pretreatment (14 days) with live A. muciniphila prior to surgical colonic perforation on peritonitis, mortality, and wound healing. We used mice with an inducible intestinal-epithelial-cell-specific deletion of MyD88 (IEC-MyD88 KO) to investigate the role of the innate immune system in this context. In a proof-of-concept pilot study, healthy humans were exposed to A. muciniphila for 2 h and colonic biopsies taken before and after colonic instillation for transcriptomic analysis. Seven days after colonic perforation, A.-muciniphila-treated mice had significantly lower mortality and severity of peritonitis. This effect was associated with significant improvements of wound histological healing scores, higher production of IL22, but no changes in the mucus layer thickness or genes involved in cell renewal, proliferation, or differentiation. All these effects were abolished in IEC-MyD88 KO mice. Finally, human subjects exposed to A. muciniphila exhibited an increased level of the bacterium at the mucus level 2 h after instillation and significant changes in the expression of different genes involved in the regulation of cell cycling, gene transcription, immunity, and inflammation in their colonic mucosa. A. muciniphila improves wound healing during transmural colonic wall defect through mechanisms possibly involving IL22 signaling and requiring MyD88 in the intestinal cells. In healthy humans, colonic administration of A. muciniphila is well tolerated and changes the expression of genes involved in the immune pathways. Full article
(This article belongs to the Special Issue The Multifaceted Microbiome in Health and Disease)
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Review

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24 pages, 813 KiB  
Review
The Implication of the Gut Microbiome in Heart Failure
by Vasile Valeriu Lupu, Anca Adam Raileanu, Cristina Maria Mihai, Ionela Daniela Morariu, Ancuta Lupu, Iuliana Magdalena Starcea, Otilia Elena Frasinariu, Adriana Mocanu, Felicia Dragan and Silvia Fotea
Cells 2023, 12(8), 1158; https://0-doi-org.brum.beds.ac.uk/10.3390/cells12081158 - 14 Apr 2023
Cited by 29 | Viewed by 3558
Abstract
Heart failure is a worldwide health problem with important consequences for the overall wellbeing of affected individuals as well as for the healthcare system. Over recent decades, numerous pieces of evidence have demonstrated that the associated gut microbiota represent an important component of [...] Read more.
Heart failure is a worldwide health problem with important consequences for the overall wellbeing of affected individuals as well as for the healthcare system. Over recent decades, numerous pieces of evidence have demonstrated that the associated gut microbiota represent an important component of human physiology and metabolic homeostasis, and can affect one’s state of health or disease directly, or through their derived metabolites. The recent advances in human microbiome studies shed light on the relationship between the gut microbiota and the cardiovascular system, revealing its contribution to the development of heart failure-associated dysbiosis. HF has been linked to gut dysbiosis, low bacterial diversity, intestinal overgrowth of potentially pathogenic bacteria and a decrease in short chain fatty acids-producing bacteria. An increased intestinal permeability allowing microbial translocation and the passage of bacterial-derived metabolites into the bloodstream is associated with HF progression. A more insightful understanding of the interactions between the human gut microbiome, HF and the associated risk factors is mandatory for optimizing therapeutic strategies based on microbiota modulation and offering individualized treatment. The purpose of this review is to summarize the available data regarding the influence of gut bacterial communities and their derived metabolites on HF, in order to obtain a better understanding of this multi-layered complex relationship. Full article
(This article belongs to the Special Issue The Multifaceted Microbiome in Health and Disease)
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20 pages, 1078 KiB  
Review
Nasal Microbiome and Its Interaction with the Host in Childhood Asthma
by Yao Zeng and Jessie Qiaoyi Liang
Cells 2022, 11(19), 3155; https://0-doi-org.brum.beds.ac.uk/10.3390/cells11193155 - 7 Oct 2022
Cited by 3 | Viewed by 2680
Abstract
Childhood asthma is a major chronic non-communicable disease in infants and children, often triggered by respiratory tract infections. The nasal cavity is a reservoir for a broad variety of commensal microbes and potential pathogens associated with respiratory illnesses including asthma. A healthy nasal [...] Read more.
Childhood asthma is a major chronic non-communicable disease in infants and children, often triggered by respiratory tract infections. The nasal cavity is a reservoir for a broad variety of commensal microbes and potential pathogens associated with respiratory illnesses including asthma. A healthy nasal microenvironment has protective effects against respiratory tract infections. The first microbial colonisation in the nasal region is initiated immediately after birth. Subsequently, colonisation by nasal microbiota during infancy plays important roles in rapidly establishing immune homeostasis and the development and maturation of the immune system. Dysbiosis of microbiota residing in the mucosal surfaces, such as the nasopharynx and guts, triggers immune modulation, severe infection, and exacerbation events. Nasal microbiome dysbiosis is related to the onset of symptomatic infections. Dynamic interactions between viral infections and the nasal microbiota in early life affect the later development of respiratory infections. In this review, we summarise the existing findings related to nasal microbiota colonisation, dynamic variations, and host–microbiome interactions in childhood health and respiratory illness with a particular examination of asthma. We also discuss our current understanding of biases produced by environmental factors and technical concerns, the importance of standardised research methods, and microbiome modification for the prevention or treatment of childhood asthma. This review lays the groundwork for paying attention to an essential but less emphasized topic and improves the understanding of the overall composition, dynamic changes, and influence of the nasal microbiome associated with childhood asthma. Full article
(This article belongs to the Special Issue The Multifaceted Microbiome in Health and Disease)
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