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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

Roadmap for embedding health equity research into learning health systems

Schoenthaler, Antoinette; Francois, Fritz; Cho, Ilseung; Ogedegbe, Gbenga
BACKGROUND:, a diverse workforce alone is not sufficient; rather holistic health equity should be established as the anchoring principal mission of all academic medical centres, residing at the intersection of clinical care, education, research and community. METHODS:, which serves as the organising framework through which we conduct embedded pragmatic research in our healthcare delivery system to target and eliminate health inequities across our tripartite mission of patient care, medical education and research. RESULTS:. These elements include: (1) developing processes for collecting accurate disaggregate data on race, ethnicity and language, sexual orientation and gender identity and disability; (2) using a data-driven approach to identify health equity gaps; (3) creating performance and metric-based quality improvement goals to measure progress toward elimination of health equity gaps; (4) investigating the root cause of the identified health equity gap; (5) developing and evaluating evidence-based solutions to address and resolve the inequities; and (6) continuous monitoring and feedback for system improvements. CONCLUSION/CONCLUSIONS:can provide a model for how academic medical centres can use pragmatic research to embed a culture of health equity into their health system.
PMID: 37328265
ISSN: 2398-631x
CID: 5613312

IDEAL: A Community-Academic-Governmental Collaboration Toward Improving Evidence-Based Data Collection on Race and Ethnicity

Kader, Farah; Ðoàn, Lan N; Chin, Matthew K; Scherer, Maya; Cárdenas, Luisa; Feng, Lloyd; Leung, Vanessa; Gundanna, Anita; Lee, Matthew; Russo, Rienna; Ogedegbe, Olugbenga G; John, Iyanrick; Cho, Ilseung; Kwon, Simona C; Yi, Stella S
PMID: 37824700
ISSN: 1545-1151
CID: 5603912

Disaggregating Racial and Ethnic Data: A Step Toward Diversity, Equity, and Inclusion

Liang, Peter S; Kwon, Simona C; Cho, Ilseung; Trinh-Shevrin, Chau; Yi, Stella
PMID: 36822735
ISSN: 1528-0012
CID: 5427462

Disaggregating Racial and Ethnic Data: A Step Toward Diversity, Equity, and Inclusion [Editorial]

Liang, Peter S; Kwon, Simona C; Cho, Ilseung; Trinh-Shevrin, Chau; Yi, Stella
PMID: 36828600
ISSN: 1542-7714
CID: 5467622

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