Professional Education


  • Doctor of Philosophy, Stanford University, MI-PHD (2014)
  • Bachelor of Science, University of California Los Angeles, Microbio., Imm. and Mol. Gen. (2008)

Stanford Advisors


All Publications


  • Transient Osmotic Perturbation Causes Long-Term Alteration to the Gut Microbiota. Cell Tropini, C., Moss, E. L., Merrill, B. D., Ng, K. M., Higginbottom, S. K., Casavant, E. P., Gonzalez, C. G., Fremin, B., Bouley, D. M., Elias, J. E., Bhatt, A. S., Huang, K. C., Sonnenburg, J. L. 2018; 173 (7): 1742

    Abstract

    Osmotic diarrhea is a prevalent condition in humans caused by food intolerance, malabsorption, and widespread laxative use. Here, we assess the resilience of the gut ecosystem to osmotic perturbation at multiple length and timescales using mice as model hosts. Osmotic stress caused reproducible extinction of highly abundant taxa and expansion of less prevalent members in human and mouse microbiotas. Quantitative imaging revealed decimation of the mucus barrier during osmotic perturbation, followed by recovery. The immune system exhibited temporary changes in cytokine levels and a lasting IgG response against commensal bacteria. Increased osmolality prevented growth of commensal strains invitro, revealing one mechanism contributing to extinction. Environmental availability of microbiota members mitigated extinction events, demonstrating how species reintroduction can affect community resilience. Our findings (1) demonstrate that even mild osmotic diarrhea can cause lasting changes to the microbiota and host and (2) lay the foundation for interventions that increase system-wide resilience.

    View details for DOI 10.1016/j.cell.2018.05.008

    View details for PubMedID 29906449

  • Competitively Selected Donor Fecal Microbiota Transplantation: Butyrate Concentration and Diversity as Measures of Donor Quality. Journal of pediatric gastroenterology and nutrition Barnes, D., Ng, K., Smits, S., Sonnenburg, J., Kassam, Z., Park, K. T. 2018

    Abstract

    In this prospective cohort study, we examine the feasibility of a protocol to optimize microbiota for fecal microbiota transplantation (FMT). Donor stool metrics generally accepted as markers of gut health were used to select a stool donor based on superior microbial diversity, balanced constitution of Bacteroidetes versus Firmicutes and high concentration of fecal butyrate. Selected donor microbiota was then administered via FMT. A total of 10 patients with median age of 12 years with recurrent Clostridium difficile infection (rCDI) received the intervention. The rate of recurrence-free resolution with 1-2 FMTs was 100% at Week 10. With a single FMT, 80% of patients cleared CDI without recurrence, while 20% of patients required a single re-treatment. No serious adverse events occurred. Microbiota sequencing revealed that recipients' gut microbiota phylogenic diversity increased by 72-hours post-transplantation, with sustainment over 10-week follow-up. This study highlights the feasibility of purposefully selecting the most ideal microbiota for transplantation.

    View details for DOI 10.1097/MPG.0000000000001940

    View details for PubMedID 29470297

  • Gut microbiome transition across a lifestyle gradient in Himalaya. PLoS biology Jha, A. R., Davenport, E. R., Gautam, Y., Bhandari, D., Tandukar, S., Ng, K. M., Fragiadakis, G. K., Holmes, S., Gautam, G. P., Leach, J., Sherchand, J. B., Bustamante, C. D., Sonnenburg, J. L. 2018; 16 (11): e2005396

    Abstract

    The composition of the gut microbiome in industrialized populations differs from those living traditional lifestyles. However, it has been difficult to separate the contributions of human genetic and geographic factors from lifestyle. Whether shifts away from the foraging lifestyle that characterize much of humanity's past influence the gut microbiome, and to what degree, remains unclear. Here, we characterize the stool bacterial composition of four Himalayan populations to investigate how the gut community changes in response to shifts in traditional human lifestyles. These groups led seminomadic hunting-gathering lifestyles until transitioning to varying levels of agricultural dependence upon farming. The Tharu began farming 250-300 years ago, the Raute and Raji transitioned 30-40 years ago, and the Chepang retain many aspects of a foraging lifestyle. We assess the contributions of dietary and environmental factors on their gut-associated microbes and find that differences in the lifestyles of Himalayan foragers and farmers are strongly correlated with microbial community variation. Furthermore, the gut microbiomes of all four traditional Himalayan populations are distinct from that of the Americans, indicating that industrialization may further exacerbate differences in the gut community. The Chepang foragers harbor an elevated abundance of taxa associated with foragers around the world. Conversely, the gut microbiomes of the populations that have transitioned to farming are more similar to those of Americans, with agricultural dependence and several associated lifestyle and environmental factors correlating with the extent of microbiome divergence from the foraging population. The gut microbiomes of Raute and Raji reveal an intermediate state between the Chepang and Tharu, indicating that divergence from a stereotypical foraging microbiome can occur within a single generation. Our results also show that environmental factors such as drinking water source and solid cooking fuel are significantly associated with the gut microbiome. Despite the pronounced differences in gut bacterial composition across populations, we found little differences in alpha diversity across lifestyles. These findings in genetically similar populations living in the same geographical region establish the key role of lifestyle in determining human gut microbiome composition and point to the next challenging steps of determining how large-scale gut microbiome reconfiguration impacts human biology.

    View details for DOI 10.1371/journal.pbio.2005396

    View details for PubMedID 30439937

  • Single-cell transcriptomics of 20 mouse organs creates a Tabula Muris. Nature 2018; 562 (7727): 367–72

    Abstract

    Here we present a compendium of single-cell transcriptomic data from the model organism Mus musculus that comprises more than 100,000 cells from 20 organs and tissues. These data represent a new resource for cell biology, reveal gene expression in poorly characterized cell populations and enable the direct and controlled comparison of gene expression in cell types that are shared between tissues, such as T lymphocytes and endothelial cells from different anatomical locations. Two distinct technical approaches were used for most organs: one approach, microfluidic droplet-based 3'-end counting, enabled the survey of thousands of cells at relatively low coverage, whereas the other, full-length transcript analysis based on fluorescence-activated cell sorting, enabled the characterization of cell types with high sensitivity and coverage. The cumulative data provide the foundation for an atlas of transcriptomic cell biology.

    View details for DOI 10.1038/s41586-018-0590-4

    View details for PubMedID 30283141

  • Toxoplasma gondii infection triggers chronic cachexia and sustained commensal dysbiosis in mice. PloS one Hatter, J. A., Kouche, Y. M., Melchor, S. J., Ng, K., Bouley, D. M., Boothroyd, J. C., Ewald, S. E. 2018; 13 (10): e0204895

    Abstract

    Toxoplasma gondii is a protozoan parasite with a predation-mediated transmission cycle between rodents and felines. Intermediate hosts acquire Toxoplasma by eating parasite cysts which invade the small intestine, disseminate systemically and finally establish host life-long chronic infection in brain and muscles. Here we show that Toxoplasma infection can trigger a severe form of sustained cachexia: a disease of progressive lean weight loss that is a causal predictor of mortality in cancer, chronic disease and many infections. Toxoplasma cachexia is characterized by acute anorexia, systemic inflammation and loss of 20% body mass. Although mice recover from symptoms of peak sickness, they fail to regain muscle mass or visceral adipose depots. We asked whether the damage to the intestinal microenvironment observed at acute time points was sustained in chronic infection and could thereby play a role in sustaining cachexia. We found that parasites replicate in the same region of the distal jejunum/proximal ileum throughout acute infection, inducing the development of secondary lymphoid structures and severe, regional inflammation. Small intestine pathology was resolved by 5 weeks post-infection. However, changes in the commensal populations, notably an outgrowth of Clostridia spp., were sustained in chronic infection. Importantly, uninfected animals co-housed with infected mice display similar changes in commensal microflora but never display symptoms of cachexia, indicating that altered commensals are not sufficient to explain the cachexia phenotype alone. These studies indicate that Toxoplasma infection is a novel and robust model to study the immune-metabolic interactions that contribute to chronic cachexia development, pathology and potential reversal.

    View details for DOI 10.1371/journal.pone.0204895

    View details for PubMedID 30379866

  • Host-Microbiota Interactions in the Pathogenesis of Antibiotic-Associated Diseases CELL REPORTS Lichtman, J. S., Ferreyra, J. A., Ng, K. M., Smits, S. A., Sonnenburg, J. L., Elias, J. E. 2016; 14 (5): 1049-1061

    Abstract

    Improved understanding of the interplay between host and microbes stands to illuminate new avenues for disease diagnosis, treatment, and prevention. Here, we provide a high-resolution view of the dynamics between host and gut microbiota during antibiotic-induced intestinal microbiota depletion, opportunistic Salmonella typhimurium and Clostridium difficile pathogenesis, and recovery from these perturbed states in a mouse model. Host-centric proteome and microbial community profiles provide a nuanced longitudinal view, revealing the interdependence between host and microbiota in evolving dysbioses. Time- and condition-specific molecular and microbial signatures are evident and clearly distinguished from pathogen-independent inflammatory fingerprints. Our data reveal that mice recovering from antibiotic treatment or C. difficile infection retain lingering signatures of inflammation, despite compositional normalization of the microbiota, and host responses could be rapidly and durably relieved through fecal transplant. These experiments demonstrate insights that emerge from the combination of these orthogonal, untargeted approaches to the gastrointestinal ecosystem.

    View details for DOI 10.1016/j.celrep.2016.01.009

    View details for Web of Science ID 000369616100009

    View details for PubMedID 26832403

  • The Enteric Two-Step: nutritional strategies of bacterial pathogens within the gut CELLULAR MICROBIOLOGY Ferreyra, J. A., Ng, K. M., Sonnenburg, J. L. 2014; 16 (7): 993-1003

    Abstract

    The gut microbiota is a dense and diverse microbial community governed by dynamic microbe-microbe and microbe-host interactions, the status of which influences whether enteric pathogens can cause disease. Here we review recent insights into the key roles that nutrients play in bacterial pathogen exploitation of the gut microbial ecosystem. We synthesize recent findings to support a five-stage model describing the transition between a healthy microbiota and one dominated by a pathogen and disease. Within this five-stage model, two stages are critical to the pathogen: (i) an initial expansion phase that must occur in the absence of pathogen-induced inflammation, followed by (ii) pathogen-promoting physiological changes such as inflammation and diarrhoea. We discuss how this emerging paradigm of pathogen life within the lumen of the gut is giving rise to novel therapeutic strategies.

    View details for DOI 10.1111/cmi.12300

    View details for Web of Science ID 000337667600002

  • Microbiota-liberated host sugars facilitate post-antibiotic expansion of enteric pathogens. Nature Ng, K. M., Ferreyra, J. A., Higginbottom, S. K., Lynch, J. B., Kashyap, P. C., Gopinath, S., Naidu, N., Choudhury, B., Weimer, B. C., Monack, D. M., Sonnenburg, J. L. 2013; 502 (7469): 96-99

    Abstract

    The human intestine, colonized by a dense community of resident microbes, is a frequent target of bacterial pathogens. Undisturbed, this intestinal microbiota provides protection from bacterial infections. Conversely, disruption of the microbiota with oral antibiotics often precedes the emergence of several enteric pathogens. How pathogens capitalize upon the failure of microbiota-afforded protection is largely unknown. Here we show that two antibiotic-associated pathogens, Salmonella enterica serovar Typhimurium (S. typhimurium) and Clostridium difficile, use a common strategy of catabolizing microbiota-liberated mucosal carbohydrates during their expansion within the gut. S. typhimurium accesses fucose and sialic acid within the lumen of the gut in a microbiota-dependent manner, and genetic ablation of the respective catabolic pathways reduces its competitiveness in vivo. Similarly, C. difficile expansion is aided by microbiota-induced elevation of sialic acid levels in vivo. Colonization of gnotobiotic mice with a sialidase-deficient mutant of Bacteroides thetaiotaomicron, a model gut symbiont, reduces free sialic acid levels resulting in C. difficile downregulating its sialic acid catabolic pathway and exhibiting impaired expansion. These effects are reversed by exogenous dietary administration of free sialic acid. Furthermore, antibiotic treatment of conventional mice induces a spike in free sialic acid and mutants of both Salmonella and C. difficile that are unable to catabolize sialic acid exhibit impaired expansion. These data show that antibiotic-induced disruption of the resident microbiota and subsequent alteration in mucosal carbohydrate availability are exploited by these two distantly related enteric pathogens in a similar manner. This insight suggests new therapeutic approaches for preventing diseases caused by antibiotic-associated pathogens.

    View details for DOI 10.1038/nature12503

    View details for PubMedID 23995682