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Fulltext Gut microbiome of pre-adolescent children of two ethnicities residing in three distant cities

Khine WWT, Zhang Y, Goie GJY, Wong MS, Liong M, Lee YY, et al.

Sci Rep, 2019 05 24;9(1):7831.
PMID: 31127186 DOI: 10.1038/s41598-019-44369-y

Recent studies have realized the link between gut microbiota and human health and diseases. The question of diet, environment or gene is the determining factor for dominant microbiota and microbiota profile has not been fully resolved, for these comparative studies have been performed on populations of different ethnicities and in short-term intervention studies. Here, the Southern Chinese populations are compared, specifically the children of Guangzhou City (China), Penang City (west coast Malaysia) and Kelantan City (east coast Malaysia). These Chinese people have similar ancestry thus it would allow us to delineate the effect of diet and ethnicity on gut microbiota composition. For comparison, the Penang and Kelantan Malay children were also included. The results revealed that differences in microbiota genera within an ethnicity in different cities was due to differences in food type. Sharing the similar diet but different ethnicity in a city or different cities and living environment showed similar gut microbiota. The major gut microbiota (more than 1% total Operational Taxonomy Units, OTUs) of the children population are largely determined by diet but not ethnicity, environment, and lifestyle. Elucidating the link between diet and microbiota would facilitate the development of strategies to improve human health at a younger age.

Matched MeSH terms: Gastrointestinal Microbiome/physiology*
Native κ-carrageenan induced-colitis is related to host intestinal microecology

Mi Y, Chin YX, Cao WX, Chang YG, Lim PE, Xue CH, et al.

Int J Biol Macromol, 2020 Mar 15;147:284-294.
PMID: 31926226 DOI: 10.1016/j.ijbiomac.2020.01.072

Inflammatory bowel disease (IBD), including Crohn's disease and ulcerative colitis, has gradually emerged as a public health challenge worldwide. Carrageenan is a popular food additive that has been in use for decades. However, controversy exists regarding to the safety of carrageenan due to its exacerbation of colitis in experimental models. In this study, we studied the effects of vehicle and host intestinal microflora on carrageenan inflammatory properties in C57BL/6 J mice. We found that in high-fat diet model, native carrageenan in drinking water increased the disease activity index (DAI), myeloperoxidase (MPO) activity and the mRNA expression of TLR4 in colon, whereas carrageenan-supplemented diet has no visible effects. However, no signs of colitis were observed under low-fat diet regardless of the mode of vehicle used. Moreover, we discovered that carrageenan-induced colitis in high-fat diet model was robustly correlated with changes in the composition of gut microbiota, specifically Alistipes finegoldii and Bacteroides acidifaciens. Hence, we propose that the inflammatory property of carrageenan is influenced greatly by its intake form via modification of host intestinal microecology.

Matched MeSH terms: Gastrointestinal Microbiome*
Fulltext Parvimonas micra, Peptostreptococcus stomatis, Fusobacterium nucleatum and Akkermansia muciniphila as a four-bacteria biomarker panel of colorectal cancer

Osman MA, Neoh HM, Ab Mutalib NS, Chin SF, Mazlan L, Raja Ali RA, et al.

Sci Rep, 2021 02 03;11(1):2925.
PMID: 33536501 DOI: 10.1038/s41598-021-82465-0

Dysbiosis of the gut microbiome has been associated with the pathogenesis of colorectal cancer (CRC). We profiled the microbiome of gut mucosal tissues from 18 CRC patients and 18 non-CRC controls of the UKM Medical Centre (UKMMC), Kuala Lumpur, Malaysia. The results were then validated using a species-specific quantitative PCR in 40 CRC and 20 non-CRC tissues samples from the UMBI-UKMMC Biobank. Parvimonas micra, Fusobacterium nucleatum, Peptostreptococcus stomatis and Akkermansia muciniphila were found to be over-represented in our CRC patients compared to non-CRC controls. These four bacteria markers distinguished CRC from controls (AUROC = 0.925) in our validation cohort. We identified bacteria species significantly associated (cut-off value of > 5 fold abundance) with various CRC demographics such as ethnicity, gender and CRC staging; however, due to small sample size of the discovery cohort, these results could not be further verified in our validation cohort. In summary, Parvimonas micra, Fusobacterium nucleatum, Peptostreptococcus stomatis and Akkermansia muciniphila were enriched in our local CRC patients. Nevertheless, the roles of these bacteria in CRC initiation and progression remains to be investigated.

Matched MeSH terms: Gastrointestinal Microbiome*
Fulltext Amelioration of high-fat diet-induced obesity and its associated complications by a myricetin derivative-rich fraction from Syzygium malaccense in C57BL/6J mice

Nallappan D, Chua KH, Ong KC, Chong CW, Teh CSJ, Palanisamy UD, et al.

Food Funct, 2021 Jul 05;12(13):5876-5891.
PMID: 34019055 DOI: 10.1039/d1fo00539a

Obesity is a driving factor in the onset of metabolic disorders. This study aims to investigate the effects of the myricetin derivative-rich fraction (MD) from Syzygium malaccense leaf extract on high-fat diet (HFD)-induced obesity and its associated complications and its influence on uncoupling protein-1 (UCP-1) and gut microbiota in C57BL/6J mice. Mice were randomly assigned into four groups (n = 6) and given a normal diet (ND) or high-fat diet (HFD) for 10 weeks to induce obesity. The HFD groups (continued with HFD) were administered 50 mg kg-1 MD (treatment), 50 mg kg-1 metformin (positive control) and normal saline (HFD and ND controls) daily for four weeks via oral gavage. The ten-week HFD-feeding resulted in hyperglycemia and elevated urinary oxidative indices. The subsequent MD administration caused significant weight reduction without appetite suppression and amelioration of insulin resistance, steatosis and dyslipidemia. Besides, MD significantly reduced lipid hydroperoxides and protein carbonyls in tissue homogenates and urine and elevated Trolox equivalent antioxidant capacity (TEAC), ferric reducing antioxidant power (FRAP) and reduced glutathione (GSH) and thus, alleviated oxidative stress. The weight reduction was correlated with downregulation of inflammatory markers and the increased UCP-1 level, suggesting weight loss plausibly through thermogenesis. The Akkermansia genus (reflects improved metabolic status) in the HFD50 group was more abundant than that in the HFD group while the non-enzymatic antioxidant markers were strongly associated with UCP-1. In conclusion, MD ameliorates obesity and its related complications possibly via the upregulation of UCP-1 and increased abundance of Akkermansia genus and is promising as a therapeutic agent in the treatment of obesity and its associated metabolic disorders.

Matched MeSH terms: Gastrointestinal Microbiome/drug effects
Fulltext A polyphenol-enriched diet and Ascaris suum infection modulate mucosal immune responses and gut microbiota composition in pigs

Williams AR, Krych L, Fauzan Ahmad H, Nejsum P, Skovgaard K, Nielsen DS, et al.

PLoS One, 2017;12(10):e0186546.
PMID: 29028844 DOI: 10.1371/journal.pone.0186546

Polyphenols are a class of bioactive plant secondary metabolites that are thought to have beneficial effects on gut health, such as modulation of mucosal immune and inflammatory responses and regulation of parasite burdens. Here, we examined the interactions between a polyphenol-rich diet supplement and infection with the enteric nematode Ascaris suum in pigs. Pigs were fed either a basal diet or the same diet supplemented with grape pomace (GP), an industrial by-product rich in polyphenols such as oligomeric proanthocyanidins. Half of the animals in each group were then inoculated with A. suum for 14 days to assess parasite establishment, acquisition of local and systemic immune responses and effects on the gut microbiome. Despite in vitro anthelmintic activity of GP-extracts, numbers of parasite larvae in the intestine were not altered by GP-supplementation. However, the bioactive diet significantly increased numbers of eosinophils induced by A. suum infection in the duodenum, jejunum and ileum, and modulated gene expression in the jejunal mucosa of infected pigs. Both GP-supplementation and A. suum infection induced significant and apparently similar changes in the composition of the prokaryotic gut microbiota, and both also decreased concentrations of isobutyric and isovaleric acid (branched-chain short chain fatty acids) in the colon. Our results demonstrate that while a polyphenol-enriched diet in pigs may not directly influence A. suum establishment, it significantly modulates the subsequent host response to helminth infection. Our results suggest an influence of diet on immune function which may potentially be exploited to enhance immunity to helminths.

Matched MeSH terms: Gastrointestinal Microbiome/drug effects*
Effect of Ipomoea aquatica ethanolic extract in streptozotocin (STZ) induced diabetic rats via1H NMR-based metabolomics approach

Abu Bakar Sajak A, Mediani A, Maulidiani, Mohd Dom NS, Machap C, Hamid M, et al.

Phytomedicine, 2017 Dec 01;36:201-209.
PMID: 29157816 DOI: 10.1016/j.phymed.2017.10.011

BACKGROUND: Ipomoea aquatica (locally known as "kangkung") has previously been reported to have hypoglycemic activities on glucose level in diabetes patients. However, the effect of I. aquatica ethanolic extract on the metabolites in the body has remained unknown.
PURPOSE: This study provides new insights on the changes of endogenous metabolites caused by I. aquatica ethanolic extract and improves the understanding on the therapeutic efficacy and mechanism of I. aquatica ethanolic extract.
METHODS: By using a combination of 1H nuclear magnetic resonance (NMR) with multivariate analysis (MVDA), the changes of metabolites due to I. aquatica ethanolic extract administration in obese diabetic-induced Sprague Dawley rats (OB+STZ+IA) were identified.
RESULTS: The results suggested 19 potential biomarkers with variable importance projections (VIP) above 0.5, which include creatine/creatinine, glucose, creatinine, citrate, carnitine, 2-oxoglutarate, succinate, hippurate, leucine, 1-methylnicotinamice (MNA), taurine, 3-hydroxybutyrate (3-HB), tryptophan, lysine, trigonelline, allantoin, formiate, acetoacetate (AcAc) and dimethylamine. From the changes in the metabolites, the affected pathways and aspects of metabolism were identified.
CONCLUSION: I. aquatica ethanolic extract increases metabolite levels such as creatinine/creatine, carnitine, MNA, trigonelline, leucine, lysine, 3-HB and decreases metabolite levels, including glucose and tricarboxylic acid (TCA) intermediates. This implies capabilities of I. aquatica ethanolic extract promoting glycolysis, gut microbiota and nicotinate/nicotinamide metabolism, improving the glomerular filtration rate (GFR) and reducing the β-oxidation rate. However, the administration of I. aquatica ethanolic extract has several drawbacks, such as unimproved changes in amino acid metabolism, especially in reducing branched chain amino acid (BCAA) synthesis pathways and lipid metabolism.

Matched MeSH terms: Gastrointestinal Microbiome/drug effects
Fulltext Palm Fruit Bioactives augment expression of Tyrosine Hydroxylase in the Nile Grass Rat basal ganglia and alter the colonic microbiome

Weinberg RP, Koledova VV, Subramaniam A, Schneider K, Artamonova A, Sambanthamurthi R, et al.

Sci Rep, 2019 Dec 09;9(1):18625.
PMID: 31819070 DOI: 10.1038/s41598-019-54461-y

Tyrosine hydroxylase (TH) catalyzes the hydroxylation of L-tyrosine to L-DOPA. This is the rate-limiting step in the biosynthesis of the catecholamines - dopamine (DA), norepinephrine (NE), and epinephrine (EP). Catecholamines (CA) play a key role as neurotransmitters and hormones. Aberrant levels of CA are associated with multiple medical conditions, including Parkinson's disease. Palm Fruit Bioactives (PFB) significantly increased the levels of tyrosine hydroxylase in the brain of the Nile Grass rat (NGR), a novel and potentially significant finding, unique to PFB among known botanical sources. Increases were most pronounced in the basal ganglia, including the caudate-putamen, striatum and substantia nigra. The NGR represents an animal model of diet-induced Type 2 Diabetes Mellitus (T2DM), exhibiting hyperglycemia, hyperinsulinemia, and insulin resistance associated with hyperphagia and accelerated postweaning weight gain induced by a high-carbohydrate diet (hiCHO). The PFB-induced increase of TH in the basal ganglia of the NGR was documented by immuno-histochemical staining (IHC). This increase in TH occurred equally in both diabetes-susceptible and diabetes-resistant NGR fed a hiCHO. PFB also stimulated growth of the colon microbiota evidenced by an increase in cecal weight and altered microbiome. The metabolites of colon microbiota, e.g. short-chain fatty acids, may influence the brain and behavior significantly.

Matched MeSH terms: Gastrointestinal Microbiome/drug effects*
Fulltext Multi-strain probiotics (Hexbio) containing MCP BCMC strains improved constipation and gut motility in Parkinson's disease: A randomised controlled trial

Ibrahim A, Ali RAR, Manaf MRA, Ahmad N, Tajurruddin FW, Qin WZ, et al.

PLoS One, 2020;15(12):e0244680.
PMID: 33382780 DOI: 10.1371/journal.pone.0244680

OBJECTIVE: We determined the effectiveness of a multi-strain probiotic (Hexbio®) containing microbial cell preparation MCP®BCMC® on constipation symptoms and gut motility in PD patients with constipation.
METHODS: PD patients with constipation (ROME III criteria) were randomized to receive a multi-strain probiotic (Lactobacillus sp and Bifidobacterium sp at 30 X 109 CFU) with fructo-oligosaccaride or placebo (fermented milk) twice daily for 8 weeks. Primary outcomes were changes in the presence of constipation symptoms using 9 items of Garrigues Questionnaire (GQ), which included an item on bowel opening frequency. Secondary outcomes were gut transit time (GTT), quality of life (PDQ39-SI), motor (MDS-UPDRS) and non-motor symptoms (NMSS).
RESULTS: Of 55 recruited, 48 patients completed the study: 22 received probiotic and 26 received placebo. At 8 weeks, there was a significantly higher mean weekly BOF in the probiotic group compared to placebo [SD 4.18 (1.44) vs SD 2.81(1.06); (mean difference 1.37, 95% CI 0.68, 2.07, uncorrected p<0.001)]. Patients in the probiotic group reported five times higher odds (odds ratio = 5.48, 95% CI 1.57, 19.12, uncorrected p = 0.008) for having higher BOF (< 3 to 3-5 to >5 times/week) compared to the placebo group. The GTT in the probiotic group [77.32 (SD55.35) hours] reduced significantly compared to placebo [113.54 (SD 61.54) hours]; mean difference -36.22, 95% CI -68.90, -3.54, uncorrected p = 0.030). The mean change in GTT was 58.04 (SD59.04) hour vs 20.73 (SD60.48) hours respectively (mean difference 37.32, 95% CI 4.00, 70.63, uncorrected p = 0.028). No between-groups differences were observed in the NMSS, PDQ39-SI, MDS-UPDRS II and MDS-UPDRS III scores. Four patients in the probiotics group experienced mild reversible side effects.
CONCLUSION: This study showed that consumption of a multi-strain probiotic (Hexbio®) over 8 weeks improved bowel opening frequency and whole gut transit time in PD patients with constipation.

Matched MeSH terms: Gastrointestinal Microbiome/drug effects*
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*
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
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*
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*
Fulltext Streptococcus mitis induces conversion of Helicobacter pylori to coccoid cells during co-culture in vitro

Khosravi Y, Dieye Y, Loke MF, Goh KL, Vadivelu J

PLoS One, 2014;9(11):e112214.
PMID: 25386948 DOI: 10.1371/journal.pone.0112214

Helicobacter pylori (H. pylori) is a major gastric pathogen that has been associated with humans for more than 60,000 years. H. pylori causes different gastric diseases including dyspepsia, ulcers and gastric cancers. Disease development depends on several factors including the infecting H. pylori strain, environmental and host factors. Another factor that might influence H. pylori colonization and diseases is the gastric microbiota that was overlooked for long because of the belief that human stomach was a hostile environment that cannot support microbial life. Once established, H. pylori mainly resides in the gastric mucosa and interacts with the resident bacteria. How these interactions impact on H. pylori-caused diseases has been poorly studied in human. In this study, we analyzed the interactions between H. pylori and two bacteria, Streptococcus mitis and Lactobacillus fermentum that are present in the stomach of both healthy and gastric disease human patients. We have found that S. mitis produced and released one or more diffusible factors that induce growth inhibition and coccoid conversion of H. pylori cells. In contrast, both H. pylori and L. fermentum secreted factors that promote survival of S. mitis during the stationary phase of growth. Using a metabolomics approach, we identified compounds that might be responsible for the conversion of H. pylori from spiral to coccoid cells. This study provide evidences that gastric bacteria influences H. pylori physiology and therefore possibly the diseases this bacterium causes.

Matched MeSH terms: Gastrointestinal Microbiome
Fulltext The Potential of Mesenchymal Stromal Cell as Therapy in Neonatal Diseases

Liau LL, Al-Masawa ME, Koh B, Looi QH, Foo JB, Lee SH, et al.

Front Pediatr, 2020;8:591693.
PMID: 33251167 DOI: 10.3389/fped.2020.591693

Mesenchymal stromal cells (MSCs) can be derived from various tissue sources, such as the bone marrow (BMSCs), adipose tissue (ADSCs), umbilical cord (UC-MSCs) and umbilical cord blood (UCB-MSCs). Clinical trials have been conducted to investigate the potential of MSCs in ameliorating neonatal diseases, including bronchopulmonary dysplasia (BPD), intraventricular hemorrhage (IVH) and necrotizing enterocolitis (NEC). In preclinical studies, MSC therapy has been tested for the treatment of various neonatal diseases affecting the heart, eye, gut, and brain as well as sepsis. Up to date, the number of clinical trials using MSCs to treat neonatal diseases is still limited. The data reported thus far positioned MSC therapy as safe with positive outcomes. However, most of these trials are still preliminary and generally smaller in scale. Larger trials with more appropriate controls and a longer follow-up period need to be conducted to prove the safety and efficacy of the therapy more conclusively. This review discusses the current application of MSCs in treating neonatal diseases, its mechanism of action and future direction of this novel therapy, including the potential of using MSC-derived extracellular vesicles instead of the cells to treat various clinical conditions in the newborn.

Matched MeSH terms: Gastrointestinal Microbiome
Developments in understanding and applying prebiotics in research and practice-an ISAPP conference paper

Scott KP, Grimaldi R, Cunningham M, Sarbini SR, Wijeyesekera A, Tang MLK, et al.

J Appl Microbiol, 2020 Apr;128(4):934-949.
PMID: 31446668 DOI: 10.1111/jam.14424

AIMS: The concept of using specific dietary components to selectively modulate the gut microbiota to confer a health benefit, defined as prebiotics, originated in 1995. In 2018, a group of scientists met at the International Scientific Association for Probiotics and Prebiotics annual meeting in Singapore to discuss advances in the prebiotic field, focussing on issues affecting functionality, research methodology and geographical differences.
METHODS AND RESULTS: The discussion ranged from examining scientific literature supporting the efficacy of established prebiotics, to the prospects for establishing health benefits associated with novel compounds, isolated from different sources.
CONCLUSIONS: While many promising candidate prebiotics from across the globe have been highlighted in preliminary research, there are a limited number with both demonstrated mechanism of action and defined health benefits as required to meet the prebiotic definition. Prebiotics are part of a food industry with increasing market sales, yet there are great disparities in regulations in different countries. Identification and commercialization of new prebiotics with unique health benefits means that regulation must improve and remain up-to-date so as not to risk stifling research with potential health benefits for humans and other animals.
SIGNIFICANCE AND IMPACT OF STUDY: This summary of the workshop discussions indicates potential avenues for expanding the range of prebiotic substrates, delivery methods to enhance health benefits for the end consumer and guidance to better elucidate their activities in human studies.

Matched MeSH terms: Gastrointestinal Microbiome
Fulltext Gut Bacteria of Water Monitor Lizard (Varanus salvator) Are a Potential Source of Antibacterial Compound(s)

Akbar N, Siddiqui R, Sagathevan K, Iqbal M, Khan NA

Antibiotics (Basel), 2019 Sep 24;8(4).
PMID: 31554316 DOI: 10.3390/antibiotics8040164

For the past few decades, there has been limited progress in the development of novel antibacterials. Previously, we postulated that the gut microbiota of animals residing in polluted environments are a forthcoming supply of antibacterials. Among various species, the water monitor lizard is an interesting species that feeds on organic waste and the carcass of wild animals. Gut microbiota of the water monitor lizard were sequestered, identified and cultivated in RPMI-1640 to produce conditioned medium (CM). Next, the antimicrobial properties of CM were evaluated versus a selection of Gram-negative (Escherichia coli K1, Serratia marcescens,Pseudomonas aeruginosa, Salmonella enterica and Klebsiella pneumoniae) and Gram-positive bacteria (Streptococcus pyogenes, methicillin-resistant Staphylococcus aureus, and Bacillus cereus). CM were partially characterized by heat inactivation at 95°C for 10 min and tested against P. aeruginosa and S. pyogenes. CM were also tested against immortalized human keratinocytes (HaCaT) cells lines. The results demonstrated that gut microbiota isolated from water monitor lizard produced molecules with remarkable bactericidal activities. To determine the identity of the active molecules, CM were subjected to Liquid Chromatography-Mass Spectrometry. Several molecules were identified belonging to the classes of flavonoids, terpenoids, alkaloids, polyhydroxy alkaloids, polyacetylenes, bisphenols, amides, oxylipin and pyrazine derivatives with known broad-spectrum antimicrobial, anti-tumour, anti-oxidant, anti-inflammatory, and analgesic attributes. Furthermore, the detailed analysis of these molecules could lead us to develop effective therapeutic antibacterials.

Matched MeSH terms: Gastrointestinal Microbiome
Fulltext Polyphenols as Prebiotics in the Management of High-Fat Diet-Induced Obesity: A Systematic Review of Animal Studies

Moorthy M, Sundralingam U, Palanisamy UD

Foods, 2021 Feb 02;10(2).
PMID: 33540692 DOI: 10.3390/foods10020299

Obesity is a disease growing at an alarming rate and numerous preclinical studies have proven the role of polyphenols in managing this disease. This systematic review explores the prebiotic effect of polyphenols in the management of obesity among animals fed on a high-fat diet. A literature search was carried out in PubMed, Scopus, CINAHL, Web of Science, and Embase databases following the PRISMA guidelines. Forty-four studies reported a significant reduction in obesity-related parameters. Most notably, 83% of the studies showed a decrease in either body weight/visceral adiposity/plasma triacylglyceride. Furthermore, 42 studies reported a significant improvement in gut microbiota (GM), significantly affecting the genera Akkermansia, Bacteroides, Blautia, Roseburia, Bifidobacteria, Lactobacillus, Alistipes, and Desulfovibrio. Polyphenols' anti-obesity, anti-hyperglycaemic, and anti-inflammatory properties were associated with their ability to modulate GM. This review supports the notion of polyphenols as effective prebiotics in ameliorating HFD-induced metabolic derangements in animal models.

Matched MeSH terms: Gastrointestinal Microbiome
Fulltext Association of antimicrobial resistance and gut microbiota composition in human and non-human primates at an urban ecotourism site

Chong CW, Alkatheeri AHS, Ali N, Tay ZH, Lee YL, Paramasivam SJ, et al.

Gut Pathog, 2020;12:14.
PMID: 32175011 DOI: 10.1186/s13099-020-00352-x

Background: The rise of nature-based ecotourism in the past decade has introduced unprecedented challenges in managing the increasing interaction between humans and animals. The potential transmission of antibiotic resistant microbes between humans and non-human primate populations is a concern due to their genetic similarity. Malaysia is well known for hotspots of wildlife diversity where non-human primates like monkeys and orangutans have become popular tourist attractions. In this study, we assessed the prevalence of antimicrobial resistant Staphylococcus aureus, Enterococcus species, and other Enterobacteriaceae in the faeces of human (HS) and two non-human primates (NHP) in Malaysia, the Long-tailed macaque (Macaca fascicularis, MF) and Silvered leaf monkey (Trachypithecus cristatus, TC). In addition, the faecal bacterial composition was profiled to evaluate the potential association between antibiotic resistant profiles and composition of gut microbiota.
Results: We tested the isolated bacteria using a selection of antibiotics. The results showed that both the number of antibiotic resistant strains and resistance level were higher in humans than NHPs. Overall, the composition of gut microbiome and pattern of antibiotic resistance showed that there was higher similarity between MF and TC, the two NHPs, than with HS. In addition, samples with higher levels of antibiotic resistance showed lower bacterial richness. Homo sapiens had the lowest bacterial diversity and yet it had higher abundance of Bacteroides. In contrast, NHPs displayed higher bacterial richness and greater prevalence of Firmicutes such as Ruminococceae and Oscillospira.
Conclusion: Higher antibiotic susceptibility in NHPs is likely related to low direct exposure to antibiotics. The lack of resistance may also suggest limited antimicrobial resistance transmission between humans and NHP. Nonetheless, continued monitoring over a long period will help mitigate the risk of anthropozoonosis and zooanthroponosis.

Matched MeSH terms: Gastrointestinal Microbiome
Fulltext Elucidating the Efficacy of Vaccination against Vibriosis in Lates calcarifer Using Two Recombinant Protein Vaccines Containing the Outer Membrane Protein K (r-OmpK) of Vibrio alginolyticus and the DNA Chaperone J (r-DnaJ) of Vibrio harveyi

Silvaraj S, Md Yasin IS, A Karim MM, Saad MZ

Vaccines (Basel), 2020 Nov 06;8(4).
PMID: 33171991 DOI: 10.3390/vaccines8040660

Recombinant cell vaccines expressing the OmpK and DnaJ of Vibrio were developed and subsequently, a vaccination efficacy trial was carried out on juvenile seabass (~5 cm; ~20 g). The fish were divided into 5 groups of 50 fish per group, kept in triplicate. Groups 1 and 2 were injected with 107 CFU/mL of the inactivated recombinant cells vaccines, the pET-32/LIC-OmpK and pET-32/LIC-DnaJ, respectively. Group 3 was similarly injected with 107 CFU/mL of inactivated E. coli BL21 (DE3), Group 4 with 107 CFU/mL of formalin killed whole cells V. harveyi, and Group 5 with PBS solution. Serum, mucus, and gut lavage were used to determine the antibody levels before all fish were challenged with V. harveyi, V. alginolyticus, and V. parahemolyticus, respectively on day 15 post-vaccination. There was significant increase in the serum and gut lavage antibody titers in the juvenile seabass vaccinated with r-OmpK vaccine. In addition, there was an up-regulation for TLR2, MyD88, and MHCI genes in the kidney and intestinal tissues of r-OmpK vaccinated fish. At the same time, r-OmpK triggered higher expression level of interleukin IL-10, IL-8, IL-1ß in the spleen, intestine, and kidney compared to r-DnaJ. Overall, r-OmpK and r-DnaJ triggered protection by curbing inflammation and strengthening the adaptive immune response. Vaccinated fish also demonstrated strong cross protection against heterologous of Vibrio isolates, the V. harveyi, V. alginolyticus, and V. parahaemolyticus. The fish vaccinated with r-OmpK protein were completely protected with a relative per cent of survival (RPS) of 90 percent against V. harveyi and 100 percent against V. alginolyticus and V. parahaemolyticus. A semi-quantitative PCR detection of Vibrio spp. from the seawater containing the seabass also revealed that vaccination resulted in reduction of pathogen shedding. In conclusion, our results suggest r-OmpK as a candidate vaccine molecule against multiple Vibrio strain to prevent vibriosis in marine fish.

Matched MeSH terms: Gastrointestinal Microbiome
Fulltext Microbiome and colorectal cancer: an overview and local perspective

Rahman Jamal

Malaysian Journal of Medicine and Health Sciences, 2019;15(108):4-4.
MyJurnal

Colorectal cancer (CRC) is an important health problem that is on the rise globally, where it is the fourth most com-mon cause of deaths from cancer. CRC is now the 2nd commonest cancer in men and 3rd commonest in women in Malaysia. Diet, lifestyle, genetics and environmental interaction, together with underlying gut conditions such as inflammatory bowel disease have been reported to contribute to the disease. In addition, the gut microbiome has also been increasingly reported to be associated with CRC development, with dysbiosis of the commensal bacteria ob-served in CRC patients. Bacterial genera such as Bacteroides, Fusobacterium and Prevotella are more commonly de-tected in CRC patients compared to healthy individuals. Nevertheless, not much is known about the gut microbiome among Malaysians with different ethnicities. In Malaysia, the Chinese has the highest incidence of CRC, followed by Malays and Indians. The reason behind this difference may be contributed by the differences in the dietary intake that could modulate the gut microbiome and contribute towards the development of CRC. The current knowledge on this field still much depends on reports from individuals of American, European, Chinese, Brazilian and Japanese descendants in origin. The oncogenic potential of bacteria was suggested to include inflammation and the produc-tion of mutagenic toxin. A significant increase in certain intestinal microbiota including the genuses Enteroccus and Streptococcus spp. was detected in the advanced stage of colorectal adenoma. However, there are discrepancies in the previous studies, where some bacteria genera might be over-reported or underestimated. It is likely that the gut microbiome differs between populations. There is also no available data on the gut microbiome of the healthy individuals, colorectal adenoma (pre-cancerous) and colorectal cancer patients in the Malaysian population. Recent advancements in next generation sequencing allow faster and more accurate determination of microbial consortium in various niches of the human body and environment. In particular, sequencing of the 16S rRNA gene with specific primers have been reported to allow accurate determination of bacterial orders commonly found in the human gut as well as for those which are not expected in the digestive system. Recent developments in gut microbiome DNA ex-traction also contributed to the robustness of gut microbiome determination and analysis. All the above will contrib-ute towards an accurate and rapid cataloging process of the Malaysian gut microbiome and also enable comparison between healthy individuals, colorectal adenoma and CRC patients of the Malaysian population.

Matched MeSH terms: Gastrointestinal Microbiome

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