In vitro gut model systems permit the growth of gut microbes outside their natural habitat and are essential to the study of gut microbiota. Systems available today are limited by a lack of scalability and flexibility in the mode of operation. Here, we describe the development of a versatile bioreactor module that can be easily adjusted for culture size and capable of sensing and controlling of environmental parameters such as pH control of culture medium, rate of influx and efflux of the culture medium, and aerobic/anaerobic atmosphere. Bioreactor modules can be operated as single units or linked in series to construct a model of a digestive tract with multiple compartments to allow the growth of microbiota in vitro. We tested the growth of synthetic and natural bacterial communities in a multicompartment continuous dynamic culture model simulation of the mammalian gut. The distal compartments of a sterile system inoculated with the synthetic bacterial community at the proximal module attained a stable bacterial density by 24 h, and all the genera present in the inoculum were firmly established in the distal modules simulating the large intestine at 5 days of continuous culture. A natural bacterial community simultaneously inoculated into the distal modules attained a stable bacterial composition at the phylum level by Day 7 of continuous culture. The findings illustrate the utility of the system to culture mixed bacterial communities which can be used to study the collective biological activities of the cultured microbiota in the absence of host influence.

Obesity is characterized by chronic systemic inflammation and enhances cancer metastasis and mortality. Obesity promotes breast cancer metastasis to lung in a neutrophil-dependent manner; however, the upstream regulatory mechanisms of this process remain unknown. Here, we show that obesity-induced monocytes underlie neutrophil activation and breast cancer lung metastasis. Using mass cytometry, obesity favors the expansion of myeloid lineages while restricting lymphoid cells within the peripheral blood. RNA sequencing and flow cytometry revealed that obesity-associated monocytes resemble professional antigen-presenting cells due to a shift in their development and exhibit enhanced MHCII expression and CXCL2 production. Monocyte induction of the CXCL2–CXCR2 axis underlies neutrophil activation and release of neutrophil extracellular traps to promote metastasis, and enhancement of this signaling axis is observed in lung metastases from obese cancer patients. Our findings provide mechanistic insight into the relationship between obesity and cancer by broadening our understanding of the interactive role that myeloid cells play in this process.

In vitro gut model systems permit the growth of gut microbes outside their natural habitat and are essential to the study of gut microbiota. Systems available today are limited by lack of scalability and flexibility in mode of operation. Here we describe the development of a versatile bioreactor module capable of sensing and controlling of environmental parameters such as pH control of culture medium, rate of influx and efflux of the culture medium, and aerobic/anaerobic atmosphere. Modules can be linked in series to construct a model of a digestive tract to allow the growth of microbiota in vitro. We tested the growth of a model bacterial community in a simulated mammalian gut model. The model attained and maintained a stable bacterial community that metabolized bile acids. The findings illustrate the utility of the model to grow to culture a mixed bacterial community and recapitulate biological activities such as bile acid metabolism in vitro.

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Microbes have been part of the diet throughout human history. In the evolution of food preservation practices, some techniques inadvertently leveraged microbial activity not only to extend the storage life but also to enhance the properties and nutritive value of foods. In the last century, a variety of bacterial species (referred to as probiotics) were found to confer health benefits to the host. The advent of high-throughput sequencing methods facilitated improved surveillance of conventional probiotics within gut microbial communities as well as fueled the deep exploration of the human gut microbiota. Metagenomic analyses along with improvements in microbial culture techniques and comprehensive functional characterization of specific microbes both in vitro and in vivo have shed new insights into the intimate relationship of the gut microbiota and its host. Recent findings suggest the potential of conventional and newly identified bacterial species in enhancing nutrient processing and holds promise in improving the efficacy of conventional nutrition intervention strategies in managing diseases as well as in the delivery of personalized nutrition therapy support.