Oyuntsetseg, Khasag

Товч нэр

Oyuntsetseg, Khasag

Бүтэн нэр

Oyuntsetseg Khasag

Латин нэр

Oyuntsetseg Khasag

Албан тушаал

Судлаач

Харьяалал

Анагаахын Шинжлэх Ухааны Үндэсний Их Сургууль

ORCID

0000-0003-3037-5922

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High Antibiotic Resistance of Helicobacter pylori and Its Associated Novel Gene Mutations among the Mongolian Population
(MDPI AG, 2020-07)
Azzaya, Dashdorj
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Gantuya, Boldbaatar
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Oyuntsetseg, Khasag
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Davaadorj, Duger
;
Matsumoto, Takashi
Mongolia has a high prevalence of Helicobacter pylori infection and the second highest incidence of gastric cancer worldwide. Thus, investigating the prevalence of antibiotic resistance and its underlying genetic mechanism is necessary. We isolated 361 H. pylori strains throughout Mongolia. Agar dilution assays were used to determine the minimum inhibitory concentrations of five antibiotics; amoxicillin, clarithromycin, metronidazole, levofloxacin, and minocycline. The genetic determinants of antibiotic resistance were identified with next-generation sequencing (NGS) and the CLC Genomics Workbench. The resistance to metronidazole, levofloxacin, clarithromycin, amoxicillin, and minocycline was 78.7%, 41.3%, 29.9%, 11.9% and 0.28%, respectively. Multidrug resistance was identified in 51.3% of the isolates investigated which were further delineated into 9 antimicrobial resistance profiles. A number of known antibiotic resistance mutations were identified including rdxA, frxA (missense, frameshift), gyrA (N87K, A88P, D91G/N/Y), 23S rRNA (A2143G), pbp1A (N562Y), and 16S rRNA (A928C). Furthermore, we detected previously unreported mutations in pbp1A (L610*) and the 23S rRNA gene (A1410G, C1707T, A2167G, C2248T, and C2922T). The degree of antibiotic resistance was high, indicating the insufficiency of standard triple therapy in Mongolia.
Scopus© Citations 36
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Gastric Microbiota in Helicobacter pylori-Negative and -Positive Gastritis Among High Incidence of Gastric Cancer Area
(MDPI AG, 2019-04)
Gantuya, Boldbaatar
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El-Serag, Hashem B
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Matsumoto, Takashi
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Ajami, Nadim J
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Oyuntsetseg, Khasag
Helicobacter pylori (H. pylori) related chronic gastritis is a well-known major etiological factor for gastric cancer development. However, H. pylori-negative gastritis (HpN) is not well described. We aimed to examine gastric mucosal microbiota in HpN compared to H. pylori-positive gastritis (HpP) and H. pylori-negative non-gastritis group (control). Here, we studied 11 subjects with HpN, 40 with HpP and 24 controls. We performed endoscopy with six gastric biopsies. Comparison groups were defined based on strict histological criteria for the disease and H. pylori diagnosis. We used 16S rRNA gene amplicon sequencing to profile the gastric microbiota according to comparison groups. These results demonstrate that the HpP group had significantly lower bacterial richness by the operational taxonomic unit (OTU) counts, and Shannon and Simpson indices as compared to HpN or controls. The linear discriminant analysis effect size analysis showed the enrichment of Firmicutes, Fusobacteria, Bacteroidetes and Actinobacteria at phylum level in the HpN group. In the age-adjusted multivariate analysis, Streptococcus sp. and Haemophilus parainfluenzae were at a significantly increased risk for HpN (odds ratio 18.9 and 12.3, respectively) based on abundance. Treponema sp. was uniquely found in HpN based on occurrence. In this paper, we conclude that Streptococcus sp., Haemophilus parainfluenzae and Treponema sp. are candidate pathogenic bacterial species for HpN. These results if confirmed may have important clinical implications.
Scopus© Citations 74
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Advantage of 16S rRNA amplicon sequencing in Helicobacter pylori diagnosis
(Wiley, 2021-06)
Gantuya, Boldbaatar
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El Serag, Hashem B
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Saruuljavkhlan, Batsaikhan
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Azzaya, Dashdorj
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Matsumoto, Takashi
BACKGROUND: 16S rRNA amplicon sequencing is an accurate method of detecting microbial infection without culture. It is unclear if sequencing has additional benefits over routine diagnostic methods for Helicobacter pylori testing. METHODS: We enrolled Mongolian volunteers with dyspepsia. Using routine diagnostic methods, positive H. pylori was defined as positive results on histology/immunohistochemistry, culture, rapid urease test, or serology; negative H. pylori was defined by negative results from all these tests. We performed 16S rRNA sequencing on gastric biopsy specimens and calculated cutoffs for operational taxonomic units (OTUs) and relative abundance (RA) to define positive results using ROC curves. RESULTS: We examined 161 individuals with a mean age of 43.6 years, and 64.6% were women. Using routine diagnostic methods, 122 (75.8%) participants were H. pylori positive, the sensitivity and specificity for 16S rRNA sequencing were 94.3% and 82.1% or 93.4% and 82.1% when cutoff values were set to 1113 (OTU number) or 4.4% RA, respectively (both p < .001). When combining the validated values, the concordance rate was high (91.1%); however, 16S rRNA sequencing had additional positive yield in 9 cases (5.6%) compared with routine diagnostic methods, and much greater additional positive yield compared to histopathology/IHC, culture, RUT, serology separately with 12 (7.4%), 37 (23.0%) and 43 (26.7%). CONCLUSION: 16S rRNA amplicon sequencing detects potentially important proportion of H. pylori-positive cases that test negative with routine diagnostic methods. The quantitative number of H. pylori can help to understand how it can be changing by diseases and RA give opportunity to understand how H. pylori communicate with other microbiota.
Scopus© Citations 27
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Study of Helicobacter pylori Isolated from a High-Gastric-Cancer-Risk Population: Unveiling the Comprehensive Analysis of Virulence-Associated Genes including Secretion Systems, and Genome-Wide Association Study
(MDPI AG, 2023-09)
Saruuljavkhlan, Batsaikhan
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Alfaray, Ricky Indra
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Oyuntsetseg, Khasag
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Gantuya, Boldbaatar
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Khangai, Ayush
BACKGROUND: The prevalence of gastric cancer in Mongolia, in East Asia, remains the highest in the world. However, most Helicobacter pylori strains in Mongolia have a less virulent Western-type CagA. We aimed to determine how H. pylori genomic variation affected gastric diseases, especially gastric cancer, based on comprehensive genome analysis. METHODS: We identified a set of 274 virulence-associated genes in H. pylori, including virulence factor and outer membrane protein (OMP) genes, the type four secretion system gene cluster, and 13 well-known virulence gene genotypes in 223 H. pylori strains and their associations with gastric cancer and other gastric diseases. We conducted a genome-wide association study on 158 H. pylori strains (15 gastric cancer and 143 non-gastric cancer strains). RESULTS: Out of 274 genes, we found 13 genes were variable depending on disease outcome, especially iron regulating OMP genes. H. pylori strains from Mongolia were divided into two main subgroups: subgroup (Sg1) with high risk and Sg2 with low risk for gastric cancer. The general characteristics of Sg1 strains are that they possess more virulence genotype genes. We found nine non-synonymous single nucleotide polymorphisms in seven genes that are linked with gastric cancer strains. CONCLUSIONS: Highly virulent H. pylori strains may adapt through host-influenced genomic variations, potentially impacting gastric carcinogenesis.
Scopus© Citations 10
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Utilization of an Automated Latex Agglutination Turbidity Assay for Assessing Gastric Mucosal Alteration during Helicobacter pylori Infection
(The Editorial Office of Gut and Liver, 2024-01)
Khangai, Ayush
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Akada, Junko
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Saruuljavkhlan, Batsaikhan
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Gantuya, Boldbaatar
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Azzaya, Dashdorj
BACKGROUND/AIMS: : A latex agglutination turbidity (LA) assay to test for serum antibodies has been approved in Japan and Korea for mass screening of Helicobacter pylori infection. In this study, we evaluated the LA assay for diagnosing H. pylori infection and predicting gastric mucosal changes in a Mongolian population. METHODS: : In total, 484 individuals were classified into H. pylori-positive (n=356) and H. pylori-negative (n=128) groups, as determined by histology and H. pylori culture. RESULTS: : The best cutoff, sensitivity, and specificity values for the LA assay were 18.35 U/mL, 74.2%, and 65.6%, respectively. The LA values in the atrophic gastritis group were statistically higher than those in the other groups (healthy, chronic gastritis, intestinal metaplasia, and gastric cancer, p<0.0001). The cutoff value to distinguish the atrophic gastritis group from the other four groups was 32.0 U/mL, and its area under the curve was 0.673, which was the highest among the E-plate, pepsinogen (PG) I, PG II, and PG I/II ratio tests in our data. The odds ratios for atrophic gastritis determined by the LA assay and PG I test in multiple logistic regression were 2.5 and 1.9, respectively, which were significantly higher than for the other tests. CONCLUSIONS: : The LA assay can determine the risk of atrophic gastritis, which in turn is a considerable risk factor for gastric cancer. We propose using this assay in combination with the PG I/II ratio to avoid missing gastric cancer patients who have a low LA value (less than 32.0 U/mL).
Scopus© Citations 3
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Exploring Alternative Treatment Choices for Multidrug-Resistant Clinical Strains of Helicobacter pylori in Mongolia
(MDPI AG, 2023-11)
Khangai, Ayush
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Saruuljavkhlan, Batsaikhan
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Azzaya, Dashdorj
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Gantuya, Boldbaatar
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Oyuntsetseg, Khasag
Helicobacter pylori is a pathogen related to severe diseases such as gastric cancer; because of rising antimicrobial-resistant strains, failure to eradicate H. pylori with antibiotics has increased worldwide. Multidrug-resistant H. pylori and gastric cancer is common in Mongolia; therefore, we aimed to explore alternative antimicrobial treatments and the genomes of resistant strains in this country. A total of 361 H. pylori strains isolated from patients in Mongolia were considered. Minimal inhibitory concentrations for two fluoroquinolones (ciprofloxacin and moxifloxacin), rifabutin, and furazolidone were determined via two-fold agar dilution. Genomic mutations in antibiotic-resistant strains were identified by next-generation sequencing using the Illumina Miseq platform and compared with genes from a reference H. pylori strain (26695). The resistance rate of H. pylori strains to quinolones was high (44% to ciprofloxacin and 42% to moxifloxacin), and resistance to rifabutin was low (0.5%); none were resistant to furazolidone. Most quinolone-resistant strains possessed gyrA gene mutations causing amino acid changes (e.g., N87K, A88P, and D91G/Y/N). While one rifabutin-resistant strain had amino acid-substituting mutations in rpoB (D530N and R701C), the other had three novel rpoB mutations; both rifabutin-resistant strains were sensitive to furazolidone. Overall, our findings suggest that rifabutin and/or furazolidone may be an alternative, effective H. pylori treatment in patients who have failed to respond to other treatment regimens.
Scopus© Citations 3
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Species-level dynamics of gastric microbiome after Helicobacter pylori eradication in high-risk Mongolian population
(2026-02)
Renchinsengee, Namsrai
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Batsaikhan, Saruuljavkhlan
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Khangai, Ayush
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Boldbaatar, Gantuya
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Luvsandagva, Bayasgalan
BACKGROUND: Species-level resolution is essential to understand gastric microbiome recovery after Helicobacter pylori eradication, yet short-read 16 S rRNA approaches often obscure clinically relevant changes. METHODS: Gastric biopsies from 121 adults in Bayan-Ölgii, Mongolia (71 H. pylori-positive, 50 H. pylori-negative) were analyzed, including nine paired pre- and post-eradication gastric biopsy samples collected six months apart, enabling exploratory longitudinal analysis. Full-length 16 S rRNA (V1-V9) sequencing was performed using the Oxford Nanopore platform with EMU taxonomic assignment (SILVA v138.1/NCBI RefSeq). Ecological changes were evaluated using diversity indices, principal coordinates analysis (PCoA) with PERMANOVA, and differential abundance testing (DESeq2, FDR < 0.05). Eradication therapy (esomeprazole-bismuth-doxycycline-levofloxacin) achieved success in 54 of 57 H. pylori-positive patients (94.7%). RESULTS: H. pylori-positive microbiomes were dominated by H. pylori (91.8% ± 3.9%) and exhibited markedly reduced diversity (Shannon = 0.44 ± 0.11) compared with H. pylori-negative samples (2.08 ± 0.25; p < 0.001). Six months after eradication, diversity increased significantly (2.17 ± 0.20; p = 0.0001), with enrichment of oral commensals including Streptococcus mitis (↑ 11.9×), Neisseria elongata (↑ 13.7×), and Prevotella melaninogenica (↑ 13.0×). However, post-eradication profiles at six months remained distinct from H. pylori-negative communities (PERMANOVA R² = 0.12; p = 0.02). In total, 174 amplicon sequence variants changed significantly, including persistence of Fusobacterium nucleatum. CONCLUSIONS: Nanopore full-length 16 S sequencing reveals fine-scale, clinically relevant shifts that are masked by partial-gene assays. Eradication rapidly restores microbial diversity, but at six months, is associated with a novel ecological equilibrium rather than complete normalization. This species-resolved approach offers a practical framework for post-eradication microbiome monitoring and may inform strategies to reduce residual gastric cancer risk in high-burden populations.
Scopus© Citations 1
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Gastric mucosal microbiota in a Mongolian population with gastric cancer and precursor conditions
(Wiley, 2020-04)
Gantuya, Boldbaatar
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El Serag, Hashem B
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Matsumoto, Takashi
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Ajami, Nadim J
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Uchida, Tomohisa
BACKGROUND: Incidence and mortality of gastric cancer (GC) are high in Mongolia despite Helicobacter pylori in the Mongolian population being less virulent. AIM: To evaluate gastric bacterial microbiota profiles in patients with GC and its precursor histological conditions. METHODS: We conducted a case-control study among 48 GC and 120 noncancer patients (20 normal gastric mucosa [control], 20 gastritis, 40 with atrophy and 40 intestinal metaplasia [IM]). We performed 16S rRNA gene amplicon sequencing and compared taxonomic and functional prediction profiles based on the diagnosis group and H pylori infection status. RESULTS: The highest overall bacterial alpha diversity metrics were observed in the control group, followed by the IM and cancer groups. The gastritis and atrophy groups had the least diversity. Lactobacilli and Enterococci were the dominant genus in several cancer patients especially in the absence of H pylori. In addition, Carnobacterium, Glutamicibacter, Paeniglutamicibacter, Fusobacterium and Parvimonas were associated with GC regardless of H pylori infection. Firmicutes were decreased in the gastritis and atrophy groups and increased in the IM and cancer groups. The functional metabolic activity of the Embden-Meyerhof-Parnas pathway and the utilization of sugar, were significantly increased in cancer group compared with the noncancer group. CONCLUSION: Microbial factors other than H pylori may play a role in Mongolian GC. We identified novel associations between GC and the genera Enterococcus, Lactobacillus, Carnobacterium, Glutamicibacter, Paeniglutamicibacter, Fusobacterium, and Parvimonas.
Scopus© Citations 98

Oyuntsetseg, Khasag

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