1.Effects of proton pump inhibitor on the human gut microbiome profile in multi-ethnic groups in Singapore.
Seok Hwee KOO ; Jing DENG ; Daphne Shih Wen ANG ; John Chen HSIANG ; Lian Shien LEE ; Shafiq AAZMI ; Elsa Haniffah Mejia MOHAMED ; Hong YANG ; Siew Yoon YAP ; Lay Kek TEH ; Mohd Zaki SALLEH ; Edmund Jon Deoon LEE ; Tiing Leong ANG
Singapore medical journal 2019;60(10):512-521
INTRODUCTION:
The objectives of this study were to examine the effects of ethnicity, gender and a proton pump inhibitor (PPI), omeprazole, on the human gut microbiome. PPIs are commonly used for the treatment of acid-related disorders. We hypothesised that PPI therapy might perturb microbial communities and alter the gut microbiome.
METHODS:
Healthy subjects of Chinese (n = 12), Malay (n = 12) and Indian (n = 10) ancestry, aged 21-37 years, were enrolled. They provided a baseline stool sample (Day 1) and were then given a course of omeprazole at therapeutic dose (20 mg daily) for seven days. Stool samples were collected again on Day 7 and 14 (one week after stopping omeprazole). Microbial DNA was extracted from the stool samples, followed by polymerase chain reaction, library construction, 16S rRNA sequencing using Illumina MiSeq, and statistical and bioinformatics analyses.
RESULTS:
The findings showed an increase in species richness (p = 0.018) after omeprazole consumption on Day 7, which reverted to baseline on Day 14. There were significant increases in the relative abundance of Streptococcus vestibularis (p = 0.0001) and Veillonella dispar (p = 0.0001) on Day 7, which diminished on Day 14. Faecalibacterium prausnitzii, Sutterella stercoricanis and Bacteroides denticanum were characteristic of Chinese, Malays and Indians, respectively. Lactobacillaceae and Bacteroides xylanisolvens were the signature taxa of male and female subjects, respectively.
CONCLUSION
The study demonstrated alterations in the gut microbiome following omeprazole treatment. This may explain the underlying pathology of increased risk of Clostridium difficile infections associated with omeprazole therapy.
2.Technology Advancement Enabling the Link of Gut Microbiota with Obesity and Metabolic Disorder
Hartini Yusof ; Mohamad Shafiq Aazmi ; Ili Ng Abdullah ; Teh Lay Kek ; Aminuddin Ahmad ; Mazlifah Omar ; Thuhairah Rahman ; Mohd Zaki Salleh
Malaysian Journal of Health Sciences 2015;13(1):77-91
Obesity is a growing epidemic due to an accelerated phase of industrialization and urbanization with the overfed people
now outnumbered the underfed. It is the major public health problem with a lot of research interest as it is associated
with many complicated chronic disorders such as type-2 diabetes, cardiovascular diseases (CVD) and cancers. A global
estimation of 2.8 million deaths per year is due to obesity and there are tremendous on-going efforts to identify hosts
and environmental factors that infl uence the cause and pathogenesis of obesity. Concerted efforts from different research
groups had successfully shown that obese subjects have altered composition of gut microbiota and transplantation of this
microbiota infl uences body weight in the germ-free recipient mice. The advancement of technology had made possible
the study of gut microbiota which was unculturable for better understanding of their impact to human health. Rapid
deep sequencing of DNA at reasonable cost through various options of platforms followed by data analysis using robust
bioinformatic tools are an important way of analysing the gut microbiome. Here we review the role of gut microbiota
which modulates host’s metabolic functions and gene expression, facilitating the extraction and storage of energy from the
ingested dietary substances and leading to body-weight gain. We will discuss on the different techniques used, focusing
on the high-defi nition technologies for the determination of the composition, function and ecology of gut microbiota. This
allows the appropriate selection of platform which becomes the key for success of subsequent research.
Obesity
3.Influence of CYP2D6 polymorphisms on symptomatology and side effects of patients with schizophrenia in Malaysia
Zalina Zahari ; Mohd Razali Salleh ; Lay Kek Teh ; Rusli Ismail
Malaysian Journal of Medical Sciences 2009;16(3):13-22
Background: Our objective was to investigate the association of CYP2D6 polymorphisms with
symptoms and side-effects of patients with schizophrenia.
Methods: The subjects were 156 patients with schizophrenia undergoing antipsychotic treatment
at a psychiatric clinic. Patients with co-morbid diagnoses of substance abuse or mental retardation were
excluded from the study. Psychopathology was evaluated using the Positive and Negative Symptoms
Scale (PANSS). Extrapyramidal side-effects and akathisia were assessed with the Simpson Angus Scale
(SAS) and the Barnes Akathisia Rating Scale (BARS), respectively. DNA was extracted from blood and
subjected to PCR-genotyping.
Results: We found that CYP2D6 polymorphisms were significantly associated with a subtotal
negative PANSS score. In addition, CYP2D6 is not related to side-effects of antipsychotic therapy, or
SAS and BARS scores. The results suggest that CYP2D6 polymorphisms may have implications in
treatment response.
Conclusions: Therefore, CYP2D6 may be a predictor for treatment outcomes of patients with
schizophrenia. However, further investigation is required to confirm these findings in a larger sample.

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