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Antibiotics in early life alter the murine colonic microbiome and adiposity

Cho, Ilseung; Yamanishi, Shingo; Cox, Laura; Methe, Barbara A; Zavadil, Jiri; Li, Kelvin; Gao, Zhan; Mahana, Douglas; Raju, Kartik; Teitler, Isabel; Li, Huilin; Alekseyenko, Alexander V; Blaser, Martin J
Antibiotics administered in low doses have been widely used as growth promoters in the agricultural industry since the 1950s, yet the mechanisms for this effect are unclear. Because antimicrobial agents of different classes and varying activity are effective across several vertebrate species, we proposed that such subtherapeutic administration alters the population structure of the gut microbiome as well as its metabolic capabilities. We generated a model of adiposity by giving subtherapeutic antibiotic therapy to young mice and evaluated changes in the composition and capabilities of the gut microbiome. Administration of subtherapeutic antibiotic therapy increased adiposity in young mice and increased hormone levels related to metabolism. We observed substantial taxonomic changes in the microbiome, changes in copies of key genes involved in the metabolism of carbohydrates to short-chain fatty acids, increases in colonic short-chain fatty acid levels, and alterations in the regulation of hepatic metabolism of lipids and cholesterol. In this model, we demonstrate the alteration of early-life murine metabolic homeostasis through antibiotic manipulation.
PMID: 22914093
ISSN: 0028-0836
CID: 177150

Altering the Intestinal Microbiota during a Critical Developmental Window Has Lasting Metabolic Consequences

Cox, Laura M; Yamanishi, Shingo; Sohn, Jiho; Alekseyenko, Alexander V; Leung, Jacqueline M; Cho, Ilseung; Kim, Sungheon G; Li, Huilin; Gao, Zhan; Mahana, Douglas; Zarate Rodriguez, Jorge G; Rogers, Arlin B; Robine, Nicolas; Loke, P'ng; Blaser, Martin J
Acquisition of the intestinal microbiota begins at birth, and a stable microbial community develops from a succession of key organisms. Disruption of the microbiota during maturation by low-dose antibiotic exposure can alter host metabolism and adiposity. We now show that low-dose penicillin (LDP), delivered from birth, induces metabolic alterations and affects ileal expression of genes involved in immunity. LDP that is limited to early life transiently perturbs the microbiota, which is sufficient to induce sustained effects on body composition, indicating that microbiota interactions in infancy may be critical determinants of long-term host metabolic effects. In addition, LDP enhances the effect of high-fat diet induced obesity. The growth promotion phenotype is transferrable to germ-free hosts by LDP-selected microbiota, showing that the altered microbiota, not antibiotics per se, play a causal role. These studies characterize important variables in early-life microbe-host metabolic interaction and identify several taxa consistently linked with metabolic alterations. PAPERCLIP:
PMID: 25126780
ISSN: 0092-8674
CID: 1132022

Inferred metagenomic comparison of mucosal and fecal microbiota from individuals undergoing routine screening colonoscopy reveals similar differences observed during active inflammation

Tang, Mei San; Poles, Jordan; Leung, Jacqueline M; Wolff, Martin J; Davenport, Michael; Lee, Soo Ching; Lim, Yvonne A L; Chua, Kek Heng; Loke, P'ng; Cho, Ilseung
Abstract The mucosal microbiota lives in close proximity with the intestinal epithelium and may interact more directly with the host immune system than the luminal/fecal bacteria. The availability of nutrients in the mucus layer of the epithelium is also very different from the gut lumen environment. Inferred metagenomic analysis for microbial function of the mucosal microbiota is possible by PICRUSt. We recently found that by using this approach, actively inflamed tissue of ulcerative colitis (UC) patients have mucosal communities enriched for genes involved in lipid and amino acid metabolism, and reduced for carbohydrate and nucleotide metabolism. Here, we find that the same bacterial taxa (e.g. Acinetobacter) and predicted microbial pathways enriched in actively inflamed colitis tissue are also enriched in the mucosa of subjects undergoing routine screening colonoscopies, when compared with paired samples of luminal/fecal bacteria. These results suggest that the mucosa of healthy individuals may be a reservoir of aerotolerant microbial communities expanded during colitis.
PMID: 25559083
ISSN: 1949-0976
CID: 1428792

Correction: Helminth Colonization Is Associated with Increased Diversity of the Gut Microbiota

Lee, Soo Ching; Tang, Mei San; Lim, Yvonne A L; Choy, Seow Huey; Kurtz, Zachary D; Cox, Laura M; Gundra, Uma Mahesh; Cho, Ilseung; Bonneau, Richard; Blaser, Martin J; Chua, Kek Heng; Loke, P'ng
[This corrects the article DOI: 10.1371/journal.pntd.0002880.].
PMID: 33826625
ISSN: 1935-2735
CID: 4839322

Linking the effects of helminth infection, diet and the gut microbiota with human whole-blood signatures

Lee, Soo Ching; Tang, Mei San; Easton, Alice V; Devlin, Joseph Cooper; Chua, Ling Ling; Cho, Ilseung; Moy, Foong Ming; Khang, Tsung Fei; Lim, Yvonne A L; Loke, P'ng
Helminth infection and dietary intake can affect the intestinal microbiota, as well as the immune system. Here we analyzed the relationship between fecal microbiota and blood profiles of indigenous Malaysians, referred to locally as Orang Asli, in comparison to urban participants from the capital city of Malaysia, Kuala Lumpur. We found that helminth infections had a larger effect on gut microbial composition than did dietary intake or blood profiles. Trichuris trichiura infection intensity also had the strongest association with blood transcriptional profiles. By characterizing paired longitudinal samples collected before and after deworming treatment, we determined that changes in serum zinc and iron levels among the Orang Asli were driven by changes in helminth infection status, independent of dietary metal intake. Serum zinc and iron levels were associated with changes in the abundance of several microbial taxa. Hence, there is considerable interplay between helminths, micronutrients and the microbiota on the regulation of immune responses in humans.
PMID: 31841569
ISSN: 1553-7374
CID: 4242162

The gut microbiome and obesity

Chapter by: Chuang, Philip; Cho, Ilseung
in: Eating disorders and obesity: A comprehensive handbook by Brownell, Kelly D [Ed]; Walsh, B
New York : Guilford Press, 2018
pp. 416-420
ISBN: 978-1-4625-2906-3
CID: 3131692


Zabar, Sondra; Phillips, Donna; Manko, Jeffrey; Buckvar-Keltz, Lynn; Ng, Grace; Fagan, Ian; Cho, Ilseung; Mack, Alexandra; Eliasz, Kinga; Andrade, Gizely N.; Kalet, Adina; Riles, Thomas S.
ISSN: 0884-8734
CID: 4449812

Integrated Analysis of Biopsies from Inflammatory Bowel Disease Patients Identifies SAA1 as a Link Between Mucosal Microbes with TH17 and TH22 Cells

Tang, Mei San; Bowcutt, Rowann; Leung, Jacqueline M; Wolff, Martin J; Gundra, Uma M; Hudesman, David; Malter, Lisa B; Poles, Michael A; Chen, Lea Ann; Pei, Zhiheng; Neto, Antonio G; Abidi, Wasif M; Ullman, Thomas; Mayer, Lloyd; Bonneau, Richard A; Cho, Ilseung; Loke, P'ng
BACKGROUND: Inflammatory bowel diseases (IBD) are believed to be driven by dysregulated interactions between the host and the gut microbiota. Our goal is to characterize and infer relationships between mucosal T cells, the host tissue environment, and microbial communities in patients with IBD who will serve as basis for mechanistic studies on human IBD. METHODS: We characterized mucosal CD4 T cells using flow cytometry, along with matching mucosal global gene expression and microbial communities data from 35 pinch biopsy samples from patients with IBD. We analyzed these data sets using an integrated framework to identify predictors of inflammatory states and then reproduced some of the putative relationships formed among these predictors by analyzing data from the pediatric RISK cohort. RESULTS: We identified 26 predictors from our combined data set that were effective in distinguishing between regions of the intestine undergoing active inflammation and regions that were normal. Network analysis on these 26 predictors revealed SAA1 as the most connected node linking the abundance of the genus Bacteroides with the production of IL17 and IL22 by CD4 T cells. These SAA1-linked microbial and transcriptome interactions were further reproduced with data from the pediatric IBD RISK cohort. CONCLUSIONS: This study identifies expression of SAA1 as an important link between mucosal T cells, microbial communities, and their tissue environment in patients with IBD. A combination of T cell effector function data, gene expression and microbial profiling can distinguish between intestinal inflammatory states in IBD regardless of disease types.
PMID: 28806280
ISSN: 1536-4844
CID: 2669222

Hypermethylation and Changes in Microbial Diversity Found in Colorectal Cancers [Meeting Abstract]

Lee, Henry; Luo, Yuying; Sullivan, Lauren; Bowman, Christopher; Chuang, Philip; Segal, Leopoldo; Snuderl, Matija; Cho, Ilseung
ISSN: 1572-0241
CID: 2492382

Corrigendum: Multi-Center Colonoscopy Quality Measurement Utilizing Natural Language Processing

Imler, Timothy D; Morea, Justin; Kahi, Charles; Cardwell, Jon; Johnson, Cynthia S; Xu, Huiping; Ahnen, Dennis; Antaki, Fadi; Ashley, Christopher; Baffy, Gyorgy; Cho, Ilseung; Dominitz, Jason; Hou, Jason; Korsten, Mark; Nagar, Anil; Promrat, Kittichai; Robertson, Douglas; Saini, Sameer; Shergill, Amandeep; Smalley, Walter; Imperiale, Thomas F
PMID: 26673514
ISSN: 1572-0241
CID: 1931032