Jun Ma

Baylor College of Medicine, Houston, Texas, United States

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Publications (33)140.86 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: The human microbiome, the collective genome of the microbial community that is on and within us, has recently been mapped. The initial characterization of healthy subjects has provided investigators with a reference population for interrogating the microbiome in metabolic, intestinal, and reproductive health and disease states. Although it is known that bacteria can colonize the vagina, recent metagenomic studies have shown that the vaginal microbiome varies among reproductive age women. Similarly, the richness and diversity of intestinal microbiota also naturally fluctuate among gravidae in both human and nonhuman primates, as well as mice. Moreover, recent evidence suggests that microbiome niches in pregnancy are not limited to maternal body sites, as the placenta appears to harbor a low biomass microbiome that is presumptively established in early pregnancy and varies in association with a remote history of maternal antenatal infection as well as preterm birth. In this article, we will provide a brief overview on metagenomics science as a means to investigate the microbiome, observations pertaining to both variation and the presumptive potential role of a varied microbiome during pregnancy, and how future studies of the microbiome in pregnancy may lend to a better understanding of human biology, reproductive health, and parturition. Copyright © 2015 Cold Spring Harbor Laboratory Press; all rights reserved.
    Cold Spring Harbor Perspectives in Medicine 03/2015; 5(6). DOI:10.1101/cshperspect.a023051 · 7.56 Impact Factor
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    ABSTRACT: Mitochondrial (mt) DNA encodes the proteins of the electron transfer chain to produce ATP through oxidative phosphorylation, and is essential to sustain life. mtDNA is unique from the nuclear genome in so much as it is solely maternally inherited (non-Mendelian patterning), and shows a relatively high rate of mutation due to the absence of error checking capacity. While it is generally assumed that most new mutations accumulate through the process of heteroplasmy, it is unknown whether mutations initiate in the mother are inherited, occur in utero, or occur and accumulate early in life. The purpose of this study is to examine the maternally heritable and de novo mutation rate in the fetal mtDNA through high fidelity sequencing from amongst a large population-based cohort. Samples were obtained from 90 matched maternal (blood) and fetal (placental) pairs. In addition, a smaller cohort (n=5) of maternal (blood)-fetal (placental)-and neonatal (cord blood) trios were subjected to DNA extraction and shotgun sequencing. The whole genome was sequenced on the Illumina HiSeq platform, andaplogroups and mtDNA variants were identified through mapping to reference mitochondrial genomes (NC_012920). We observed 665 single nucleotide polymorphisms (SNP) and 82 indel variants identified in the cohort at large. We achieved high sequencing depth of the mtDNA to an average depth of 65X (range 20-171X) coverage. The proportions of haplogroups identified in the cohort are consistent with the patient's self-identified ethnicity (>90% Hispanic), and all maternal-fetal pairs mapped to the identical haplogroup. Only variants from samples with average depth >20X and allele frequency >1% were included for further analysis. While the majority of the maternal-fetal pairs (>90%) demonstrated identical variants at the single nucleotide level, we observed rare mtSNP discordance between maternal and fetal mitochondrial genomes. In this first in depth sequencing analysis of mtDNA from maternal-fetal pairs at the time of birth, a low rate of de novo mutations appear in the fetal mitochondrial genome. This implies that thesemutations likely arise from the maternal heteroplasmic pool (such as in the oocyte), and accumulate later in the offsprings life. These findings have key implications for both the occurrence and screening for mitochondrial disorders. Copyright © 2015 Elsevier Inc. All rights reserved.
    American Journal of Obstetrics and Gynecology 02/2015; 212(1). DOI:10.1016/j.ajog.2015.02.009 · 3.97 Impact Factor
  • American Journal of Obstetrics and Gynecology 01/2015; 212(1):S153. DOI:10.1016/j.ajog.2014.10.328 · 3.97 Impact Factor
  • American Journal of Obstetrics and Gynecology 01/2015; 212(1):S56. DOI:10.1016/j.ajog.2014.10.125 · 3.97 Impact Factor
  • American Journal of Obstetrics and Gynecology 01/2015; 212(1):S39-S40. DOI:10.1016/j.ajog.2014.10.103 · 3.97 Impact Factor
  • American Journal of Obstetrics and Gynecology 01/2015; 212(1):S53-S54. DOI:10.1016/j.ajog.2014.10.124 · 3.97 Impact Factor
  • American Journal of Obstetrics and Gynecology 01/2015; 212(1):S78-S79. DOI:10.1016/j.ajog.2014.10.168 · 3.97 Impact Factor
  • American Journal of Obstetrics and Gynecology 01/2015; 212(1):S10. DOI:10.1016/j.ajog.2014.10.059 · 3.97 Impact Factor
  • American Journal of Obstetrics and Gynecology 01/2015; 212(1):S181. DOI:10.1016/j.ajog.2014.10.388 · 3.97 Impact Factor
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    ABSTRACT: While a higher maternal BMI is associated with preterm birth, it is unclear whether excess gestational weight gain (GWG) or obesity drives increased risk. We and others have shown that the placenta harbors microbiota, which are significantly different among preterm births. Our aim in this study was to investigate whether the preterm placental microbiome varies by virtue of obesity or alternately by excess GWG. Placentas (n=320) were collected from term and preterm gravidae. Genomic DNA was extracted and subjected to metagenomic sequencing. Data was analyzed by clinical covariates, including the 2009 Institute of Medicine's GWG guideline and obesity. Analysis of 16S rRNA-based metagenomics revealed no clustering of the microbiome by virtue of obesity (p=0.161). Among gravidae who spontaneously delivered preterm, there was again no clustering by obesity (p=0.480), but there was significant clustering by excess GWG (p=0.022). Moreover, among preterm births, detailed analysis identified microbial genera (family and genus level) and bacterial metabolic gene pathways that varied among gravidae with excess GWG. Notably, excess GWG was associated with decreased microbial folate biosynthesis pathways and decreased butanoate metabolism (LDA >3.0-fold). Although there were no significant alterations in the microbiome by virtue of obesity per se, excess GWG was associated with an altered microbiome and its metabolic profile among those who experienced a preterm birth. Copyright © 2014 Elsevier Inc. All rights reserved.
    American Journal of Obstetrics and Gynecology 12/2014; 212(5). DOI:10.1016/j.ajog.2014.12.041 · 3.97 Impact Factor
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    ABSTRACT: Humans and their microbiomes have coevolved as a physiologic community composed of distinct body site niches with metabolic and antigenic diversity. The placental microbiome has not been robustly interrogated, despite recent demonstrations of intracellular bacteria with diverse metabolic and immune regulatory functions. A population-based cohort of placental specimens collected under sterile conditions from 320 subjects with extensive clinical data was established for comparative 16S ribosomal DNA-based and whole-genome shotgun (WGS) metagenomic studies. Identified taxa and their gene carriage patterns were compared to other human body site niches, including the oral, skin, airway (nasal), vaginal, and gut microbiomes from nonpregnant controls. We characterized a unique placental microbiome niche, composed of nonpathogenic commensal microbiota from the Firmicutes, Tenericutes, Proteobacteria, Bacteroidetes, and Fusobacteria phyla. In aggregate, the placental microbiome profiles were most akin (Bray-Curtis dissimilarity <0.3) to the human oral microbiome. 16S-based operational taxonomic unit analyses revealed associations of the placental microbiome with a remote history of antenatal infection (permutational multivariate analysis of variance, P = 0.006), such as urinary tract infection in the first trimester, as well as with preterm birth <37 weeks (P = 0.001).
    Science translational medicine 05/2014; 6(237):237ra65. DOI:10.1126/scitranslmed.3008599 · 14.41 Impact Factor
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    ABSTRACT: The intestinal microbiome is a unique ecosystem and an essential mediator of metabolism and obesity in mammals. However, studies investigating the impact of the diet on the establishment of the gut microbiome early in life are generally lacking, and most notably so in primate models. Here we report that a high-fat maternal or postnatal diet, but not obesity per se, structures the offspring's intestinal microbiome in Macaca fuscata (Japanese macaque). The resultant microbial dysbiosis is only partially corrected by a low-fat, control diet after weaning. Unexpectedly, early exposure to a high-fat diet diminished the abundance of non-pathogenic Campylobacter in the juvenile gut, suggesting a potential role for dietary fat in shaping commensal microbial communities in primates. Our data challenge the concept of an obesity-causing gut microbiome and rather provide evidence for a contribution of the maternal diet in establishing the microbiota, which in turn affects intestinal maintenance of metabolic health.
    Nature Communications 05/2014; 5:3889. DOI:10.1038/ncomms4889 · 10.74 Impact Factor
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    ABSTRACT: Data from animal models show that in utero exposure to a maternal high-fat diet (HFD) renders susceptibility of these offspring to the adult onset of metabolic syndrome. We and others have previously shown that epigenetic modifications to histones may serve as a molecular memory of the in utero exposure, rendering the risk of adult disease. Because mice heterozygous for the Glut4 gene (insulin sensitive glucose transporter) born to wild-type (WT) mothers demonstrate exacterbated metabolic syndrome when exposed to an HFD in utero, we sought to analyze the genome-wide epigenetic changes that occur in the fetal liver in susceptible offspring. WT and Glut4(+/-) (G4(+/-)) offspring of WT mothers that were exposed either to a control or an HFD in utero were studied. Immunoblotting was used to measure hepatic histone modifications of fetal and 5-week animals. Chromatin immunoprecipitation (ChIP) followed by hybridization to chip arrays (ChIP-on-chip) was used to detect genome-wide changes of histone modifications with HFD exposure. We found that levels of hepatic H3K14ac and H3K9me3 significantly increased with HFD exposure in WT and G4(+/-) fetal and 5-week offspring. Pathway analysis of our ChIP-on-chip data revealed differential H3K14ac and H3K9me3 enrichment along pathways that regulate lipid metabolism, specifically in the promoter regions of Pparg, Ppara, Rxra, and Rora. We conclude that HFD exposure in utero is associated with functional alterations to fetal hepatic histone modifications in both WT and G4(+/-) offspring, some of which persist up to 5 weeks of age.
    American journal of obstetrics and gynecology 05/2014; 210(5):463.e1-463.e11. DOI:10.1016/j.ajog.2014.01.045 · 3.97 Impact Factor
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    ABSTRACT: Although our microbial community and genomes (the human microbiome) outnumber our genome by several orders of magnitude, to what extent the human host genetic complement informs the microbiota composition is not clear. The Human Microbiome Project (HMP) Consortium established a unique population-scale framework with which to characterize the relationship of microbial community structure with their human hosts. A wide variety of taxa and metabolic pathways have been shown to be differentially distributed by virtue of race/ethnicity in the HMP. Given that mtDNA haplogroups are the maternally derived ancestral genomic markers and mitochondria's role as the generator for cellular ATP, characterizing the relationship between human mtDNA genomic variants and microbiome profiles becomes of potential marked biologic and clinical interest. We leveraged sequencing data from the HMP to investigate the association between microbiome community structures with its own host mtDNA variants. 15 haplogroups and 631 mtDNA nucleotide polymorphisms (mean sequencing depth of 280X on the mitochondria genome) from 89 individuals participating in the HMP were accurately identified. 16S rRNA (V3-V5 region) sequencing generated microbiome taxonomy profiles and whole genome shotgun sequencing generated metabolic profiles from various body sites were treated as traits to conduct association analysis between haplogroups and host clinical metadata through linear regression. The mtSNPs of individuals with European haplogroups were associated with microbiome profiles using PLINK quantitative trait associations with permutation and adjusted for multiple comparisons. We observe that among 139 stool and 59 vaginal posterior fornix samples, several haplogroups show significant association with specific microbiota (q-value < 0.05) as well as their aggregate community structure (Chi-square with Monte Carlo, p < 0.005), which confirmed and expanded previous research on the association of race and ethnicity with microbiome profile. Our results further indicate that mtDNA variations may render different microbiome profiles, possibly through an inflammatory response to different levels of reactive oxygen species activity. These data provide initial evidence for the association between host ancestral genome with the structure of its microbiome.
    BMC Genomics 04/2014; 15(1):257. DOI:10.1186/1471-2164-15-257 · 4.04 Impact Factor
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    ABSTRACT: Whole genome shotgun sequencing (WGS) has been increasingly recognized as the most comprehensive and robust approach for metagenomics research. When compared with 16S-based metagenomics, it offers the advantage of identification of species level taxonomy and the estimation of metabolic pathway activities from human and environmental samples. Several large-scale metagenomic projects have been recently conducted or are currently underway utilizing WGS. With the generation of vast amounts of data, the bioinformatics and computational analysis of WGS results become vital for the success of a metagenomics study. However, each step in the WGS data analysis, including metagenome assembly, gene prediction, taxonomy identification, function annotation, and pathway analysis, is complicated by the shear amount of data. Algorithms and tools have been developed specifically to handle WGS-generated metagenomics data with the hope of reducing the requirement on computational time and storage space. Here, we present an overview of the current state of metagenomics through WGS sequencing, challenges frequently encountered, and up-to-date solutions. Several applications that are uniquely applicable to microbiome studies in reproductive and perinatal medicine are also discussed.
    Seminars in Reproductive Medicine 01/2014; 32(1):5-13. DOI:10.1055/s-0033-1361817 · 3.00 Impact Factor
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    ABSTRACT: Dysbiosis of the microbiome has been associated with type II diabetes mellitus, obesity, inflammatory bowel disorders, and colorectal cancer, and recently, the Human Microbiome Project Consortium has helped to define a healthy microbiome. Now research has begun to investigate how the microbiome is established, and in this article, we will discuss the maternal influences on the establishment of the microbiome. The inoculation of an individual's microbiome is highly dependent on the maternal microbiome, and changes occur in the maternal microbiome during pregnancy that may help to shape the neonatal microbiome. Further, we consider how mode of delivery may shape the developing microbiome of a neonate, and we end by discussing how the microbiome may impact preterm birth and the possibility of bacterial colonization of the placenta. Although the current literature demonstrates that the transformation of the maternal microbiome during pregnancy effects the establishment of the neonatal microbiome, further research is needed to explore how the microbiome shapes our metabolism and developing immune system.
    Seminars in Reproductive Medicine 01/2014; 32(1):14-22. DOI:10.1055/s-0033-1361818 · 3.00 Impact Factor
  • American Journal of Obstetrics and Gynecology 01/2014; 210(1):S221. DOI:10.1016/j.ajog.2013.10.469 · 3.97 Impact Factor
  • American Journal of Obstetrics and Gynecology 01/2014; 210(1):S30. DOI:10.1016/j.ajog.2013.10.077 · 3.97 Impact Factor
  • American Journal of Obstetrics and Gynecology 01/2014; 210(1):S45-S46. DOI:10.1016/j.ajog.2013.10.102 · 3.97 Impact Factor
  • 60th Annual Scientific Meeting of the; 03/2013