THE GUT MICROBIOME
EXPLORING COMPLEX MICROBIAL COMMUNITIES

We address fundamental biological questions, including those relevant to human health, using the gut microbiome -- a great model system.

INTERACTIONS
What makes natural microbial communities robust? What governs the stability of different states in microbial communities? How do microbes modulate their environment and thereby their host?

SYSTEMS + CONTROL

What physical principles govern the dynamics of microbial communities? What principles govern how these communities affect their hosts? How do physicochemical effects shape microbial environments? How do gut microbiota influence host physiology/ behavior?

CULTIVATION
How can we culture “unculturable” microbes?

We use innovative methods, such as...

IMAGING + BIOINFORMATICS ANALYSES
FISH, RNA-seq, real-time imaging, bioinformatics

CONTROL OF THE MICROENVIRONMENT
Splitting SlipChips, droplets, gene- and function-based microbial isolation, anaerobic chambers, gnotobiotic animals

MICROFLUIDICS
Microfabrication, device design, microfluidic culture, single-cell recovery, culture, treatment, nucleic acid extraction and single-cell gene expression

POLYMER PHYSICS

DEVELOPING MORE HUMAN-LIKE MOUSE MODELS

 

 

SOME OF OUR MOST RECENT PUBLICATIONS IN THIS FIELD

Said R. Bogatyrev, Justin C. Rolando, and Rustem F. Ismagilov. 2020. "Self-reinoculation with fecal flora changes microbiota density and composition leading to an altered bile-acid profile in the mouse small intestine." Microbiome. 8(19):1-22.

In coprophagic mice, continuous self-exposure to the fecal flora had substantial quantitative and qualitative effects on the upper gastrointestinal microbiome. These differences in microbial abundance and community composition were associated with an altered profile of the small intestine bile acid pool, and, importantly, could not be inferred from analyzing large intestine or stool samples. Overall, the patterns observed in the small intestine of non-coprophagic mice (reduced total microbial load, low abundance of anaerobic microbiota, and bile acids predominantly in the conjugated form) resemble those typically seen in the human small intestine.

"Poop Matters: Making the Mouse Gut Microbiome More Human-Like" Caltech Matters, February 2020

 

Preska Steinberg et al. 2019. "High-molecular-weight polymers from dietary fiber drive aggregation of particulates in the murine small intestine." eLife. 8:e40387.

The lumen of the small intestine (SI) is filled with particulates: microbes, therapeutic particles, and food granules. The structure of this particulate suspension could impact uptake of drugs and nutrients and the function of microorganisms. Here, we demonstrate that particles spontaneously aggregate in SI luminal fluid ex vivo. We find that aggregation can be controlled using polymers from dietary fiber in a manner that is qualitatively consistent with polymer-induced depletion interactions. Furthermore, we find that aggregation is tunable; by feeding mice dietary fibers of different molecular weights, we can control aggregation in SI luminal fluid. This work suggests that the molecular weight and concentration of dietary polymers play an underappreciated role in shaping the physicochemical environment of the gut.

Large dietary fibre molecules change gut microbiome New Food Magazine, 2/30/19

 

 

 

 

 

 

Datta et al. 2016. Polymers in the gut compress the colonic mucus hydrogel. PNAS. 113(26):7041-7046.

Colonic mucus is a key biological hydrogel that protects the gut from infection and physical damage and mediates host–microbe interactions and drug delivery. Here, we demonstrate that gut polymers ... regulate mucus hydrogel structure, and that polymer–mucus interactions can be described using a thermodynamic model based on Flory–Huggins solution theory. We found that both dietary and therapeutic polymers dramatically compressed murine colonic mucus ex vivo and in vivo.

"Dietary Fiber and Microbes" NEWS STORY

 

 

 

 

 

 

 

Yano et al. 2015. Indigenous Bacteria from the Gut Microbiota Regulate Host Serotonin Biosynthesis. Cell  161 (2). pp. 264-276.

The gastrointestinal (GI) tract contains much of the body’s serotonin (5-hydroxytryptamine, 5-HT), but mechanisms controlling the metabolism of gut-derived 5-HT remain unclear. Here, we demonstrate that the microbiota plays a critical role in regulating host 5-HT.

Ma et al. 2014. Gene-targeted Microfluidic Cultivation Validated by Isolation of a Gut Bacterium Listed in Human Microbiome Project's Most Wanted taxa. PNAS 111(27):9768-9773.

This paper describes a microfluidics-based workflow for genetically targeted isolation and cultivation of microorganisms from complex clinical samples. … Here, we describe a method that enables genetically targeted cultivation of microorganisms through a combination of microfluidics and on- and off-chip assays. We validated this targeted approach by cultivating a bacterium, here referred to as isolate microfluidicus 1, from a human cecal biopsy. Isolate microfluidicus 1 is, to our knowledge, the first successful example of targeted cultivation of a microorganism from the high-priority group of the Human Microbiome Project’s “Most Wanted” list.

“Busted!” NEWS STORY LINK

Ma et al. 2014. Individually addressable arrays of replica microbial cultures enabled by splitting SlipChips. Integr. Biol. 6(8):796-805.

Isolating microbes carrying genes of interest from environmental samples involves the use of genetic assays that often require lysis of microbial cells, which is not compatible with the goal of obtaining live cells for isolation and culture. This paper describes the design, fabrication, biological validation, and underlying physics of a microfluidic SlipChip device that addresses this challenge.

We are currently hiring postdoctoral researchers for all areas of microbiome research!

Please see our "Positions" page for more details.