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  1. Fulltext Mycobiome in the Gut: A Multiperspective Review
    Chin VK, Yong VC, Chong PP, Amin Nordin S, Basir R, Abdullah M
    Mediators Inflamm, 2020;2020:9560684.
    PMID: 32322167 DOI: 10.1155/2020/9560684
    Human gut is home to a diverse and complex microbial ecosystem encompassing bacteria, viruses, parasites, fungi, and other microorganisms that have an undisputable role in maintaining good health for the host. Studies on the interplay between microbiota in the gut and various human diseases remain the key focus among many researchers. Nevertheless, advances in sequencing technologies and computational biology have helped us to identify a diversity of fungal community that reside in the gut known as the mycobiome. Although studies on gut mycobiome are still in its infancy, numerous sources have reported its potential role in host homeostasis and disease development. Nonetheless, the actual mechanism of its involvement remains largely unknown and underexplored. Thus, in this review, we attempt to discuss the recent advances in gut mycobiome research from multiple perspectives. This includes understanding the composition of fungal communities in the gut and the involvement of gut mycobiome in host immunity and gut-brain axis. Further, we also discuss on multibiome interactions in the gut with emphasis on fungi-bacteria interaction and the influence of diet in shaping gut mycobiome composition. This review also highlights the relation between fungal metabolites and gut mycobiota in human homeostasis and the role of gut mycobiome in various human diseases. This multiperspective review on gut mycobiome could perhaps shed new light for future studies in the mycobiome research area.
    Matched MeSH terms: Gastrointestinal Microbiome/genetics
  2. Fulltext Geographical separation and ethnic origin influence the human gut microbial composition: a meta-analysis from a Malaysian perspective
    Dwiyanto J, Ayub Q, Lee SM, Foo SC, Chong CW, Rahman S
    Microb Genom, 2021 Aug;7(8).
    PMID: 34463609 DOI: 10.1099/mgen.0.000619
    Ethnicity is consistently reported as a strong determinant of human gut microbiota. However, the bulk of these studies are from Western countries, where microbiota variations are mainly driven by relatively recent migration events. Malaysia is a multicultural society, but differences in gut microbiota persist across ethnicities. We hypothesized that migrant ethnic groups continue to share fundamental gut traits with the population in the country of origin due to shared cultural practices despite subsequent geographical separation. To test this hypothesis, the 16S rRNA gene amplicons from 16 studies comprising three major ethnic groups in Malaysia were analysed, covering 636 Chinese, 248 Indian and 123 Malay individuals from four countries (China, India, Indonesia and Malaysia). A confounder-adjusted permutational multivariate analysis of variance (PERMANOVA) detected a significant association between ethnicity and the gut microbiota (PERMANOVA R2=0.005, pseudo-F=2.643, P=0.001). A sparse partial least squares - discriminant analysis model trained using the gut microbiota of individuals from China, India and Indonesia (representation of Chinese, Indian and Malay ethnic group, respectively) showed a better-than-random performance in classifying Malaysian of Chinese descent, although the performance for Indian and Malay were modest (true prediction rate, Chinese=0.60, Indian=0.49, Malay=0.44). Separately, differential abundance analysis singled out Ligilactobacillus as being elevated in Indians. We postulate that despite the strong influence of geographical factors on the gut microbiota, cultural similarity due to a shared ethnic origin drives the presence of a shared gut microbiota composition. The interplay of these factors will likely depend on the circumstances of particular groups of migrants.
    Matched MeSH terms: Gastrointestinal Microbiome/genetics*
  3. Fulltext Geography as non-genetic modulation factor of chicken cecal microbiota
    Pin Viso N, Redondo E, Díaz Carrasco JM, Redondo L, Sabio Y Garcia J, Fernández Miyakawa M, et al.
    PLoS One, 2021;16(1):e0244724.
    PMID: 33406150 DOI: 10.1371/journal.pone.0244724
    The gastrointestinal tract of chickens harbors a highly diverse microbiota contributing not only to nutrition, but also to the physiological development of the gastrointestinal tract. Microbiota composition depends on many factors such as the portion of the intestine as well as the diet, age, genotype, or geographical origin of birds. The aim of the present study was to demonstrate the influence of the geographical location over the cecal microbiota from broilers. We used metabarcoding sequencing datasets of the 16S rRNA gene publicly available to compare the composition of the Argentine microbiota against the microbiota of broilers from another seven countries (Germany, Australia, Croatia, Slovenia, United States of America, Hungary, and Malaysia). Geographical location played a dominant role in shaping chicken gut microbiota (Adonis R2 = 0.6325, P = 0.001; Mantel statistic r = 0.1524, P = 4e-04) over any other evaluated factor. The geographical origin particularly affected the relative abundance of the families Bacteroidaceae, Lactobacillaceae, Lachnospiraceae, Ruminococcaceae, and Clostridiaceae. Because of the evident divergence of microbiota among countries we coined the term "local microbiota" as convergent feature that conflates non-genetic factors, in the perspective of human-environmental geography. Local microbiota should be taken into consideration as a native overall threshold value for further appraisals when testing the production performance and performing correlation analysis of gut microbiota modulation against different kind of diet and/or management approaches. In this regard, we described the Argentine poultry cecal microbiota by means of samples both from experimental trials and commercial farms. Likewise, we were able to identify a core microbiota composed of 65 operational taxonomic units assigned to seven phyla and 38 families, with the four most abundant taxa belonging to Bacteroides genus, Rikenellaceae family, Clostridiales order, and Ruminococcaceae family.
    Matched MeSH terms: Gastrointestinal Microbiome/genetics*
  4. Fulltext Development of qPCR platform with probes for quantifying prevalent and biomedically relevant human gut microbial taxa
    Kurina I, Popenko A, Klimenko N, Koshechkin S, Chuprikova L, Filipenko M, et al.
    Mol Cell Probes, 2020 Aug;52:101570.
    PMID: 32304824 DOI: 10.1016/j.mcp.2020.101570
    Nowadays the advent of innovative high-throughput sequencing allows obtaining high-quality microbiome profiling. However, PCR-based tests are still considered the "golden standard" for many clinical applications. Here, we designed a qPCR-based platform with fluorescent-labeled oligonucleotide probes for assessing human gut microbiome composition. The system allows conducting qualitative and semiquantitative analysis for 12 prokaryotic taxa that are prevalent in the human gut and associated with diseases, diet, age and other factors. The platform was validated by comparing microbiome profile data obtained with two different methods - the platform and high-throughput 16S rRNA sequencing - across 42 stool samples. The test can form the basis for precise and cost-efficient microbiome assay for large-scale surveys including clinical trials with interventions related to diet and disease risks.
    Matched MeSH terms: Gastrointestinal Microbiome/genetics*
  5. Fulltext Comparative assessment of faecal microbial composition and metabonome of swine, farmers and human control
    Tan SC, Chong CW, Yap IKS, Thong KL, Teh CSJ
    Sci Rep, 2020 Jun 02;10(1):8997.
    PMID: 32488118 DOI: 10.1038/s41598-020-65891-4
    The gastrointestinal tract of humans and swine consist of a wide range of bacteria which interact with hosts metabolism. Due to the differences in co-evolution and co-adaptation, a large fraction of the gut microbiome is host-specific. In this study, we evaluated the effect of close human-animal interaction to the faecal metagenome and metabonome of swine, farmer and human control. Three distinct clusters were observed based on T-RFLP-derived faecal microbial composition. However, 16S-inferred faecal microbiota and metabolic profiles showed that only human control was significantly different from the swine (P 
    Matched MeSH terms: Gastrointestinal Microbiome/genetics
  6. Fulltext The gut virome in two indigenous populations from Malaysia
    Lee CZ, Zoqratt MZHM, Phipps ME, Barr JJ, Lal SK, Ayub Q, et al.
    Sci Rep, 2022 Feb 03;12(1):1824.
    PMID: 35115615 DOI: 10.1038/s41598-022-05656-3
    The human gut contains a complex microbiota dominated by bacteriophages but also containing other viruses and bacteria and fungi. There are a growing number of techniques for the extraction, sequencing, and analysis of the virome but currently no standardized protocols. This study established an effective workflow for virome analysis to investigate the virome of stool samples from two understudied ethnic groups from Malaysia: the Jakun and Jehai Orang Asli. By using the virome extraction and analysis workflow with the Oxford Nanopore Technology, long-read sequencing successfully captured close to full-length viral genomes. The virome composition of the two indigenous Malaysian communities were remarkably different from those found in other parts of the world. Additionally, plant viruses found in the viromes of these individuals were attributed to traditional food-seeking methods. This study establishes a human gut virome workflow and extends insights into the healthy human gut virome, laying the groundwork for comparative studies.
    Matched MeSH terms: Gastrointestinal Microbiome/genetics*
  7. Metagenomics analysis reveals significant modulation of cecal microbiota of broilers fed palm kernel expeller diets
    Chen WL, Tang SGH, Jahromi MF, Candyrine SCL, Idrus Z, Abdullah N, et al.
    Poult Sci, 2019 Jan 01;98(1):56-68.
    PMID: 30137571 DOI: 10.3382/ps/pey366
    The potential use of palm kernel expeller (PKE) as an alternative energy source in broiler diets is limited by the high fiber content. Although enzymatic treatment could alleviate the fiber component and increase the nutritive value of PKE, this apparent improvement is not reflected in the growth response of birds fed with the treated-PKE. As chicken's ceca are the most heavily populated with microflora within their gastrointestinal tract, it was hypothesized that any modulation of the intestinal environment by dietary treatments should be reflected by the composition and activities of the cecal microflora. There is a correlation between cecal microbiota composition and the efficiency of the host to extract energy from the diet and to deposit that energy into improved feed conversion ratio. At present, little is known about the changes on cecal microflora of broilers fed with PKE diets. Hence, this study was designed to assess the effects of feeding different forms of PKE; namely untreated PKE (UPKE), enzyme-treated PKE (EPKE), and oligosaccharides extracted from PKE (OligoPKE), on the cecal microbiota of broiler chickens at 14 d old (day 14) and 28 d old (day 28) using 16S rRNA gene high-throughput next-generation sequencing method. The results showed that temporal changes in cecal microbiota of broiler chickens were evident on day 14 and day 28. The relative abundance of phylum Firmicutes, known to be involved in nutrient uptake and absorption in both age groups was higher in the UPKE as compared to EPKE group. In addition, supplementation of OligoPKE increased (P < 0.05) the relative abundance of Lactobacillus on both D14 and D28, signifying its effect as prebiotics in enhancing growth of indigenous Lactobacillus. Our results showed that cecal microbiota was significantly modulated by dietary treatments and that the lower relative abundance of phylum Firmicutes in chickens fed with EPKE could be a reason why broiler chickens fed with EPKE of higher metabolizable energy (ME) content did not show improvement in their growth performance.
    Matched MeSH terms: Gastrointestinal Microbiome/genetics
  8. Guidelines for Transparency on Gut Microbiome Studies in Essential and Experimental Hypertension
    Marques FZ, Jama HA, Tsyganov K, Gill PA, Rhys-Jones D, Muralitharan RR, et al.
    Hypertension, 2019 12;74(6):1279-1293.
    PMID: 31679421 DOI: 10.1161/HYPERTENSIONAHA.119.13079
    Hypertension is a complex and modifiable condition in which environmental factors contribute to both onset and progression. Recent evidence has accumulated for roles of diet and the gut microbiome as environmental factors in blood pressure regulation. However, this is complex because gut microbiomes are a unique feature of each individual reflecting that individual's developmental and environmental history creating caveats for both experimental models and human studies. Here, we describe guidelines for conducting gut microbiome studies in experimental and clinical hypertension. We provide a complete guide for authors on proper design, analyses, and reporting of gut microbiota/microbiome and metabolite studies and checklists that can be used by reviewers and editors to support robust reporting and interpretation. We discuss factors that modulate the gut microbiota in animal (eg, cohort, controls, diet, developmental age, housing, sex, and models used) and human studies (eg, blood pressure measurement and medication, body mass index, demographic characteristics including age, cultural identification, living structure, sex and socioeconomic environment, and exclusion criteria). We also provide best practice advice on sampling, storage of fecal/cecal samples, DNA extraction, sequencing methods (including metagenomics and 16S rRNA), and computational analyses. Finally, we discuss the measurement of short-chain fatty acids, metabolites produced by the gut microbiota, and interpretation of data. These guidelines should support better transparency, reproducibility, and translation of findings in the field of gut microbiota/microbiome in hypertension and cardiovascular disease.
    Matched MeSH terms: Gastrointestinal Microbiome/genetics*
  9. Fulltext Enrichment of gut-derived Fusobacterium is associated with suboptimal immune recovery in HIV-infected individuals
    Lee SC, Chua LL, Yap SH, Khang TF, Leng CY, Raja Azwa RI, et al.
    Sci Rep, 2018 09 24;8(1):14277.
    PMID: 30250162 DOI: 10.1038/s41598-018-32585-x
    We explored the gut microbiota profile among HIV-infected individuals with diverse immune recovery profiles following long-term suppressive ART and investigated the relationship between the altered bacteria with markers of immune dysfunction. The microbiota profile of rectal swabs from 26 HIV-infected individuals and 20 HIV-uninfected controls were examined. Patients were classified as suboptimal responders, sIR (n = 10, CD4 T-cell <350 cells/ul) and optimal responders, oIR (n = 16, CD4 T-cell >500 cells/ul) after a minimum of 2 years on suppressive ART. Canonical correlation analysis(CCA) and multiple regression modelling were used to explore the association between fecal bacterial taxa abundance and immunological profiles in optimal and suboptimal responders. We found Fusobacterium was significantly enriched among the HIV-infected and the sIR group. CCA results showed that Fusobacterium abundance was negatively correlated with CD4 T-cell counts, but positively correlated with CD4 T-cell activation and CD4 Tregs. Multiple linear regression analysis adjusted for age, baseline CD4 T-cell count, antibiotic exposure and MSM status indicated that higher Fusobacterium relative abundance was independently associated with poorer CD4 T-cell recovery following ART. Enrichment of Fusobacterium was associated with reduced immune recovery and persistent immune dysfunction following ART. Modulating the abundance of this bacterial taxa in the gut may be a viable intervention to improve immune reconstitution in our setting.
    Matched MeSH terms: Gastrointestinal Microbiome/genetics
  10. Fulltext Physical fitness in community-dwelling older adults is linked to dietary intake, gut microbiota, and metabolomic signatures
    Castro-Mejía JL, Khakimov B, Krych Ł, Bülow J, Bechshøft RL, Højfeldt G, et al.
    Aging Cell, 2020 03;19(3):e13105.
    PMID: 31967716 DOI: 10.1111/acel.13105
    When humans age, changes in body composition arise along with lifestyle-associated disorders influencing fitness and physical decline. Here we provide a comprehensive view of dietary intake, physical activity, gut microbiota (GM), and host metabolome in relation to physical fitness of 207 community-dwelling subjects aged +65 years. Stratification on anthropometric/body composition/physical performance measurements (ABPm) variables identified two phenotypes (high/low-fitness) clearly linked to dietary intake, physical activity, GM, and host metabolome patterns. Strikingly, despite a higher energy intake high-fitness subjects were characterized by leaner bodies and lower fasting proinsulin-C-peptide/blood glucose levels in a mechanism likely driven by higher dietary fiber intake, physical activity and increased abundance of Bifidobacteriales and Clostridiales species in GM and associated metabolites (i.e., enterolactone). These factors explained 50.1% of the individual variation in physical fitness. We propose that targeting dietary strategies for modulation of GM and host metabolome interactions may allow establishing therapeutic approaches to delay and possibly revert comorbidities of aging.
    Matched MeSH terms: Gastrointestinal Microbiome/genetics*
  11. Fulltext Effects of a Lactobacillus salivarius mixture on performance, intestinal health and serum lipids of broiler chickens
    Shokryazdan P, Faseleh Jahromi M, Liang JB, Ramasamy K, Sieo CC, Ho YW
    PLoS One, 2017;12(5):e0175959.
    PMID: 28459856 DOI: 10.1371/journal.pone.0175959
    The ban or severe restriction on the use of antibiotics in poultry feeds to promote growth has led to considerable interest to find alternative approaches. Probiotics have been considered as such alternatives. In the present study, the effects of a Lactobacillus mixture composed from three previously isolated Lactobacillus salivarius strains (CI1, CI2 and CI3) from chicken intestines on performance, intestinal health status and serum lipids of broiler chickens has been evaluated. Supplementation of the mixture at a concentration of 0.5 or 1 g kg-1 of diet to broilers for 42 days improved body weight, body weight gain and FCR, reduced total cholesterol, LDL-cholesterol and triglycerides, increased populations of beneficial bacteria such as lactobacilli and bifidobacteria, decreased harmful bacteria such as E. coli and total aerobes, reduced harmful cecal bacterial enzymes such as β-glucosidase and β-glucuronidase, and improved intestinal histomorphology of broilers. Because of its remarkable efficacy on broiler chickens, the L. salivarius mixture could be considered as a good potential probiotic for chickens, and its benefits should be further evaluated on a commercial scale.
    Matched MeSH terms: Gastrointestinal Microbiome/genetics
  12. Fulltext Detection and characterization of ESBL-producing Enterobacteriaceae from the gut of healthy chickens, Gallus gallus domesticus in rural Nepal: Dominance of CTX-M-15-non-ST131 Escherichia coli clones
    Hosuru Subramanya S, Bairy I, Nayak N, Amberpet R, Padukone S, Metok Y, et al.
    PLoS One, 2020;15(5):e0227725.
    PMID: 32469888 DOI: 10.1371/journal.pone.0227725
    The surge in the prevalence of drug-resistant bacteria in poultry is a global concern as it may pose an extended threat to humans and animal health. The present study aimed to investigate the colonization proportion of extended-spectrum β-lactamase (ESBL) and carbapenemase-producing Enterobacteriaceae (EPE and CPE, respectively) in the gut of healthy poultry, Gallus gallus domesticus in Kaski district of Western Nepal. Total, 113 pooled rectal swab specimens from 66 private household farms and 47 commercial poultry farms were collected by systematic random sampling from the Kaski district in western Nepal. Out of 113 pooled samples, 19 (28.8%) samples from 66 backyard farms, and 15 (31.9%) from 47 commercial broiler farms were positive for EPE. Of the 38 EPE strains isolated from 34 ESBL positive rectal swabs, 31(81.6%) were identified as Escherichia coli, five as Klebsiella pneumoniae (13.2%), and one each isolate of Enterobacter species and Citrobacter species (2.6%). Based on genotyping, 35/38 examined EPE strains (92.1%) were phylogroup-1 positive, and all these 35 strains (100%) had the CTX-M-15 gene and strains from phylogroup-2, and 9 were of CTX-M-2 and CTX-M-14, respectively. Among 38 ESBL positive isolates, 9 (23.7%) were Ambler class C (Amp C) co-producers, predominant were of DHA, followed by CIT genes. Two (6.5%) E. coli strains of ST131 belonged to clade C, rest 29/31 (93.5%) were non-ST131 E. coli. None of the isolates produced carbapenemase. Twenty isolates (52.6%) were in-vitro biofilm producers. Univariate analysis showed that the odd of ESBL carriage among commercial broilers were 1.160 times (95% CI 0.515, 2.613) higher than organically fed backyard flocks. This is the first study in Nepal, demonstrating the EPE colonization proportion, genotypes, and prevalence of high-risk clone E. coli ST131 among gut flora of healthy poultry. Our data indicated that CTX-M-15 was the most prevalent ESBL enzyme, mainly associated with E. coli belonging to non-ST131clones and the absence of carbapenemases.
    Matched MeSH terms: Gastrointestinal Microbiome/genetics*
  13. Fulltext Temporal changes in gut microbiota profile in children with acute lymphoblastic leukemia prior to commencement-, during-, and post-cessation of chemotherapy
    Chua LL, Rajasuriar R, Lim YAL, Woo YL, Loke P, Ariffin H
    BMC Cancer, 2020 Feb 24;20(1):151.
    PMID: 32093640 DOI: 10.1186/s12885-020-6654-5
    BACKGROUND: Alteration in gut microbiota has been recently linked with childhood leukemia and the use of chemotherapy. Whether the perturbed microbiota community is restored after disease remission and cessation of cancer treatment has not been evaluated. This study examines the chronological changes of gut microbiota in children with acute lymphoblastic leukemia (ALL) prior to the start-, during-, and following cessation of chemotherapy.

    METHODOLOGY: We conducted a longitudinal observational study in gut microbiota profile in a group of paediatric patients diagnosed with ALL using 16 s ribosomal RNA sequencing and compared these patients' microbiota pattern with age and ethnicity-matched healthy children. Temporal changes of gut microbiota in these patients with ALL were also examined at different time-points in relation to chemotherapy.

    RESULTS: Prior to commencement of chemotherapy, gut microbiota in children with ALL had larger inter-individual variability compared to healthy controls and was enriched with bacteria belonging to Bacteroidetes phylum and Bacteroides genus. The relative abundance of Bacteroides decreased upon commencement of chemotherapy. Restitution of gut microbiota composition to resemble that of healthy controls occurred after cessation of chemotherapy. However, the microbiota composition (beta diversity) remained distinctive and a few bacteria were different in abundance among the patients with ALL compared to controls despite completion of chemotherapy and presumed restoration of normal health.

    CONCLUSION: Our findings in this pilot study is the first to suggest that gut microbiota profile in children with ALL remains marginally different from healthy controls even after cessation of chemotherapy. These persistent microbiota changes may have a role in the long-term wellbeing in childhood cancer survivors but the impact of these changes in subsequent health perturbations in these survivors remain unexplored.

    Matched MeSH terms: Gastrointestinal Microbiome/genetics*
  14. Gut Microbial Ecosystem in Parkinson Disease: New Clinicobiological Insights from Multi-Omics
    Tan AH, Chong CW, Lim SY, Yap IKS, Teh CSJ, Loke MF, et al.
    Ann Neurol, 2021 03;89(3):546-559.
    PMID: 33274480 DOI: 10.1002/ana.25982
    OBJECTIVE: Gut microbiome alterations in Parkinson disease (PD) have been reported repeatedly, but their functional relevance remains unclear. Fecal metabolomics, which provide a functional readout of microbial activity, have scarcely been investigated. We investigated fecal microbiome and metabolome alterations in PD, and their clinical relevance.

    METHODS: Two hundred subjects (104 patients, 96 controls) underwent extensive clinical phenotyping. Stool samples were analyzed using 16S rRNA gene sequencing. Fecal metabolomics were performed using two platforms, nuclear magnetic resonance (NMR) spectroscopy and liquid chromatography-mass spectrometry.

    RESULTS: Fecal microbiome and metabolome composition in PD was significantly different from controls, with the largest effect size seen in NMR-based metabolome. Microbiome and NMR-based metabolome compositional differences remained significant after comprehensive confounder analyses. Differentially abundant fecal metabolite features and predicted functional changes in PD versus controls included bioactive molecules with putative neuroprotective effects (eg, short chain fatty acids [SCFAs], ubiquinones, and salicylate) and other compounds increasingly implicated in neurodegeneration (eg, ceramides, sphingosine, and trimethylamine N-oxide). In the PD group, cognitive impairment, low body mass index (BMI), frailty, constipation, and low physical activity were associated with fecal metabolome compositional differences. Notably, low SCFAs in PD were significantly associated with poorer cognition and low BMI. Lower butyrate levels correlated with worse postural instability-gait disorder scores.

    INTERPRETATION: Gut microbial function is altered in PD, characterized by differentially abundant metabolic features that provide important biological insights into gut-brain pathophysiology. Their clinical relevance further supports a role for microbial metabolites as potential targets for the development of new biomarkers and therapies in PD. ANN NEUROL 2021;89:546-559.

    Matched MeSH terms: Gastrointestinal Microbiome/genetics*
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