Biology subjects

Dominguez-Bello, M. G.

Publications and source records attributed to Dominguez-Bello, M. G..

5 recordsLinked to original sources

bioRxiv2026

Urea is a dynamic and functional component of mammalian breast milk

Urea is a constituent of human milk, yet its regulation and interactions with the infant gut microbiome remain unclear. Combining three human cohorts, a controlled mouse model, and complementary microbiome analyses, we show that milk urea increases across lactation, is conserved across mammals, and is not explained by circulating urea levels or maternal diet. Instead, we identify lactation-dependent remodeling of mammary urea-metabolism and transport pathways, including dynamic AQP3 localization in secretory epithelium, indicative of regulated transfer of circulating urea into breast milk. Alongside urea, maternal milk and stool provide complementary reservoirs of urea-metabolizing bacteria that help establish the infant "ureabiome", whose urea-utilization capacity is supported by metagenomics. This maternal-infant axis is context-dependent: infant formulas provide substantially higher urea levels than human milk, while functional assays show that urea supports both commensal and opportunistic bacteria in a concentration-dependent manner. Together, these findings define a maternal nitrogen axis through which lactation can shape the assembly and function of the infant gut microbiome.

microbiology↗

bioRxiv2026

Dietary fiber selectively regulates intestinal persistence of probiotic bifidobacteria

Bifidobacteria dominate the gut microbiota of breast-fed infants, and are strongly associated with human health, including immune regulation, colonization resistance, and protection against inflammation. However, bifidobacteria persist at high abundance after weaning in only a subset of individuals, and the factors that regulate intestinal persistence of bifidobacteria are poorly understood. Using gnotobiotic mouse models, we identified a common dietary fiber, raffinose, as a critical determinant of bifidobacterial persistence during microbial transitions associated with weaning. Bifidobacterial persistence depends on an intact raffinose utilization operon and is associated with disease resistance and restrained inflammation in adult mice. Specific dietary fiber recommendations commencing at weaning are a potential strategy to maintain bifidobacteria persistence beyond infancy, with potential long-term benefits for host resilience and reduced risk of inflammatory disease.

microbiology↗

bioRxiv2025

Evaluating long-term stool preservation methods for maximizing the recovery of viable human fecal microbiota

The gut microbiome plays a fundamental role in human health, prompting efforts to catalogue and preserve its diversity across human populations. While DNA sequencing dominates microbiome research, cultivation remains essential for mechanistic studies and therapeutic development. Yet, best practices for long-term stool preservation remain limited. Here, we compared the stability of eight cryopreservation treatments for maintaining viable stool microbiota over a 1-year storage period at -80{degrees}C (freezer) or at -196{degrees}C (liquid nitrogen), using samples from infants, children, and adults. Combining cultivation on six media with 16S rRNA sequencing, we show that ultralow temperature cryopreservation has minimal impact on microbiota diversity compared to fresh cultures. Standard glycerol preservation and simple snap-freezing performed comparably to more complex and costly protocols, with all cultured samples retaining donor-specific microbiota profiles also after long-term cryopreservation. The lack of strong treatment-specific effects on microbiota composition suggest a shared microbial response to freeze-thaw stress favoring fast-growing taxa. Our findings offer practical, low-cost strategies for stool biobanking. ImportanceThe cultivation of bacterial taxa from complex communities, such as those in fecal samples, is essential for mechanistic studies and the development of microbiota-based therapeutics, including defined consortia and individual probiotic strains. Such cultivation efforts typically rely on previously stored samples; however, systematic knowledge regarding long-term preservation strategies that ensure viability and regrowth of constituent bacterial taxa remains limited. In this study, we systematically evaluated 16 distinct cryopreservation conditions to assess their efficacy in maintaining bacterial viability. Our results show that conventional glycerol-based preservation and simple snap-freezing are comparable in performance to more elaborate and cost-intensive protocols. Moreover, we identified the duration of sample transport prior to freezing as a critical determinant of post-thaw bacterial recovery. These findings provide valuable data on the relative effectiveness of various preservation methods and support the use of low-cost, easily implementable strategies that are particularly suitable for application in resource-limited settings.

microbiology↗

bioRxiv2025

Gut microbiota phospholipids regulate intestinal gene expression and can counteract the effects of antibiotic treatment

The gut microbiome influences immune and metabolic homeostasis. Our research using non-obese diabetic (NOD) mice revealed that early-life antibiotic exposure remodels the gut microbiome affecting metabolism and accelerating type 1 diabetes (T1D) incidence, with cecal material transplant (CMT) mitigating the damage. Now examining murine intestinal lipidomic profiles, we identified 747 compounds. Comparing the lipidomic profiles of cecal contents of conventional and germ-free mice and their diets, we identified 87 microbially-produced lipids reduced by antibiotic exposure but CMT-restored. Parallel analysis of human fecal lipid profiles after azithromycin-exposure showed significant alterations with substantial overlap with mice. In vitro co-culture with mouse macrophages or small intestinal epithelial cells and human colonic epithelial cells identified phospholipids that repress inflammation through the NF{kappa}B pathway. Oral administration of these phospholipids to antibiotic-treated NOD mice reduced expression of ileal genes involved in early stages of T1D pathogenesis. These findings indicate potential therapeutic anti-inflammatory roles of microbially-produced lipids.

microbiology↗

bioRxiv2018

Links between environment, diet, and the hunter-gatherer microbiome

The study of traditional populations provides a view of human-associated microbes unperturbed by industrialization, as well as a window into the microbiota that co-evolved with humans. Here we discuss our recent work characterizing the microbiota from the Hadza hunter-gatherers of Tanzania. We found seasonal shifts in bacterial taxa, diversity, and carbohydrate utilization by the microbiota. When compared to the microbiota composition from other populations around the world, the Hadza microbiota shares bacterial families with other traditional societies that are rare or absent from microbiotas of industrialized nations. We present additional observations from the Hadza microbiota and their lifestyle and environment, including microbes detected on hands, water, and animal sources, how the microbiota varies with sex and age, and the shortterm effects of introducing agricultural products into the diet. In the context of our previously published findings and of these additional observations, we discuss a path forward for future work.

microbiology↗