Decoding the microbiome to restore immune balance and transform care in multiple sclerosis, cancer, and chronic inflammatory disease.
We humans have evolved as holobionts, organisms whose biology is shaped not only by our own genome but also by the microbial communities (microbiome) that live within and on us. These microbes play essential roles in human physiology, including educating the immune system and maintaining the balance between tolerance and inflammation. Using a bedside-to-bench-to-bedside approach, we integrate human microbiome profiling with mechanistic studies in immune cells, organoids, and animal models to define how microbial communities and their metabolites shape immune function, mucosal homeostasis, and host responses in health and disease.
Most commensal microbes function as beneficial symbionts (“good” bugs), supporting immune training, barrier integrity, and metabolic balance. Key symbionts such as Prevotella and Bifidobacterium are consistently depleted in inflammatory diseases, particularly multiple sclerosis (MS), where their loss is associated with impaired immune regulation. Microbes, however, are not inherently fixed as good or bad, the commensal organism can switch into a pathogenic state (“bad” bug or pathobiont) when the local environment changes. Inflammation itself accelerates this shift, creating ecological pressure that reduces symbionts and enriches pathobionts, fueling a self-reinforcing cycle of immune activation. A striking example is Akkermansia muciniphila , often beneficial in metabolic health, but in MS becomes enriched and associated with Th1/Th17-driven neuroinflammation. Factors such as diet, cytokine milieu, HLA genetics, hormones, infections, and environmental exposures influence these good-to-bad functional switches. Defining the drivers of this microbial imbalance, and strategies to restore symbionts while limiting pathobionts, is central to rebuilding immune homeostasis.
Our laboratory focuses on how these context-dependent microbiome-immune interactions shape diseases such as MS. We also study how HLA class-II polymorphism (strongest genetic association with MS risk), diet, sex hormones, and environmental exposures reshape microbial communities toward tolerance or chronic inflammation. We extend these principles to cancer immunobiology as well as to understanding how environmental toxicants disrupt the microbiome to alter immune homeostasis.
Mission
To decode context-dependent microbiome-immune interactions and translate these insights into precision nutrition, beneficial microbial therapeutics, and personalized immune-modulating approaches that restore homeostasis and transform care for multiple sclerosis, cancer, and other immune-mediated diseases.
Vision
To enable a future where an individual’s microbiome can guide personalized strategies to prevent disease, restore immune balance, and promote lifelong health.
Research projects
The Gut Microbiome and Multiple Sclerosis (MS)
In this project, we investigate how gut microbial communities influence immune responses and neuroinflammation in MS. Across multiple independent human cohorts, we have shown that people with MS harbor distinct bacterial and fungal microbiome profiles compared to matched controls, and that the ratio of symbionts to pathobionts, e.g., the Bifidobacterium to Akkermansia ratio, correlates with disease presence, severity, and progression. Using pseudo-germ-free mice, we have validated the functional significance of these microbes by demonstrating that transferring microbiota enriched or depleted in people with MS (PwMS) induces pro-inflammatory immune signatures and modulate disease severity, establishing a causal role rather than a simple association. Together, these studies support the development of microbiome-informed biomarkers (including symbiont:pathobiont ratios) and therapeutic strategies aimed at restoring immune regulation and reducing neuroinflammation in MS.
Microbiota-Derived Metabolites and Immune Regulation in EAE/MS
Microbial metabolites help determine whether the immune system maintains tolerance or shifts toward chronic inflammation. In MS, we find a loss of phytoestrogen-metabolizing bacteria (e.g., Prevotella, Parabacteroides, Adlercreutzia), and restoring these microbes through an isoflavone-rich diet increases anti-inflammatory metabolites and reduces neuroinflammation in EAE. We are also examining additional microbiota-derived metabolites (such as fucosylated glycans and myo-inositol phosphate derivatives) that may similarly promote immune regulation. This work supports precision nutrition strategies that leverage diet–microbe co-metabolism to reinforce immune balance in MS.
BRUGs as Therapeutics: Beneficial Bacteria as Drugs
We have developed BRUGs (Beneficial bacteria as drugs) as next-generation immunotherapies. The human commensal Prevotella is consistently reduced in MS and inversely associated with severe MS disease and IL-17A levels. Additionally, In preclinical models, Prevotella species suppress neuroinflammation, characterized by increased regulatory T cells (Tregs) and reduced pathogenic Th1/Th17 responses, effectively ameliorating disease. These findings highlight Prevotella as a promising therapeutic microbe capable of restoring immune balance in MS.
HLA Class II polymorphism, Gut Microbiome, and Neuroinflammation
We use human HLA class II transgenic mouse models to determine how MS-associated HLA alleles shape T-cell specificity, cytokine responses, and susceptibility to neuroinflammation. We have identified distinct encephalitogenic epitopes in MOG and PLP that drive disease in specific HLA-DR and -DQ backgrounds and demonstrated that HLA-DQ alleles can synergize with or exacerbate DR3-mediated disease through IL-17A/GM-CSF–driven inflammation. Recently, we showed that HLA class II polymorphisms also modulate gut microbiota composition, linking genetic risk to mucosal immune tone and CNS autoimmunity. These studies reveal a genetics → microbiome → immune response axis central to the pathobiology of MS.
Oral Microbiome and the Mouth-Gut-Brain Axis in MS
The oral cavity is a key mucosal immune site and the second most diverse microbial community in the body, yet it has been underexplored in MS. We have identified distinct oral microbiome and salivary metabolite differences in MS, including loss of early-colonizing beneficial bacteria and reduced neuroprotective metabolites such as hypotaurine. These shifts parallel inflammatory signatures in the gut, supporting a broader mucosal immune imbalance. Because saliva is simple and non-invasive to collect, the oral microbiome offers a promising biomarker source. Ongoing work uses longitudinal sampling, preclinical models, and organoid–immune co-culture platforms to determine whether MS-associated oral microbes act as drivers or indicators of inflammation, and to explore oral microbiome restoration as a therapeutic strategy.
Sex Hormones and Immune Modulation
During pregnancy, levels of estrogen and natural progesterone rise and are associated with reduced MS disease activity, suggesting both hormones contribute to immune regulation. While the immunomodulatory role of estrogen is well established, the role of progesterone, and how it compares to the many synthetic progestins commonly used in clinical settings, is far less understood. In this project, we investigate whether synthetic progestins can replicate the immune-regulatory effects of natural progesterone or whether some may instead exert neutral or pro-inflammatory effects. We also examine whether progesterone is required for the full immune-modulating effects of estrogen, given that both hormones increase during pregnancy. Together, these studies aim to define how natural and synthetic hormonal environments shape immune tolerance versus inflammation in MS.
Gut Microbiome in Environmental Toxicant–Mediated Toxicity
A number of environmental chemicals, such as glyphosate, have been linked to adverse health effects, yet the mechanisms remain unclear—especially because some toxicants do not directly target human cells. However, humans exist as a holobiont, where our biology is shaped not only by our own cells but also by the microbiome. Thus, toxicants may influence health indirectly, by altering the gut microbiota (dysbiosis), which can shift immune balance and inflammatory pathways. Our work demonstrates that exposure to environmental toxicants reduces beneficial gut bacteria and increases pro-inflammatory immune signaling, identifying the gut microbiome as a mechanistic link between environmental exposure and immune-mediated health effects.
Microbiome Contributions to Cancer Risk and Progression
We investigate how gut microbiome composition and microbial metabolism influence cancer risk, tumor behavior, and anti-tumor immunity, with a current focus on breast and colorectal cancers. Our studies reveal a consistent loss of short-chain fatty acid–producing symbionts in breast cancer, a shift linked to systemic inflammation and impaired immune surveillance. In colorectal cancer, we identify tumor-site and age-associated microbial signatures, including enrichment of pro-inflammatory taxa that influence epithelial signaling pathways, tumor microenvironment, and local immune tone. We are also determining how the microbiome shapes response and toxicity to cancer therapies, including immunotherapy, with the goal of identifying microbial predictors of treatment response. This work supports the development of microbiome-based biomarkers and therapeutic strategies, including microbial modulation to enhance anti-tumor immunity and improve cancer outcomes.