The Lineup

Our motivation to consume sugars is thought to arise at the surface of the gut. However, the neural circuits are unknown. The Bohórquez Laboratory discovered a neural circuit linking gut to brain in one synapse. The circuit begins with a type of sensory epithelial cell that synapses with the vagus nerve. These epithelial cells are called neuropod cells. In the mouse small intestine, monosynaptic rabies virus infects neuropod cells and spreads onto vagal neurons that project to the nucleus tractus solitarius in the brainstem. This neural circuit is necessary and sufficient to transduce sensory signals from sugars. Silencing neuropod cells silences the ability of the animal to distinguish the caloric content in sugars. This gut sensor for caloric sugars is a portal for nutrients to drive our motivation to eat. More recently, our laboratory has discovered that these same neural circuit in different locations of the digestive tract through the use of distinct receptors and transmitters also guide appetitive choices driven by other nutrients and microbial molecular patterns.

Elaine Hsiao

(she/her)

Director, UCLA Goodman-Luskin Microbiome Center

Associate Professor in Integrative Biology & Physiology

University of California, Los Angeles

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Toward evidence-based microbiome interventions for neurological disorders

The microbiome is increasingly recognized as a modulator of neuronal activity and development, raising the question of whether microbiome-based interventions can be developed to treat neurological and neurodevelopmental disorders. In this talk, I will use two well-characterized dietary gut-brain interactions -- the ketogenic diet for refractory epilepsy and the neurotoxic methylmercury-containing diet for impaired cognitive development -- to illustrate how native and engineered gut microbes may be used to develop evidence-based interventions to enhance treatment and thwart risk for neurological disease.

KC Huang

(he/him)

Professor of Bioengineering and of Microbiology and Immunology

Stanford University

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Physiological impact of the small intestinal microbiome

The small intestine (SI) harbors a distinct and dynamic microbial ecosystem whose composition, metabolite milieu, and interactions with the host differ markedly from those inferred from stool. To address the knowledge gap regarding SI microbiome function, we have developed an ingestible sampling device that captures luminal contents along the SI from humans in a normal digestive state. Multi-omic analyses reveal strong spatial gradients in microbiota composition, bile acid transformations, host proteome signatures, and prophage induction, all of which are poorly represented when sampling stool alone. Building on these insights, our recent work explores therapeutic modulation of the SI microbiome, especially in the context of irritable bowel syndrome (IBS) associated with pathobionts. We isolated a Klebsiella strain from the small intestine of an IBS patient and tested found that communities of SI-enriched microbes are capable of clearing Klebsiella from the SI, whereas colon-enriched microbes – mimicking typical FMTs – fail to do so. These results suggest that SI-specific microbial taxa or functions are crucial for suppression or displacement of this opportunistic pathogen in its niche. Importantly, because the SI is the first site of nutrient absorption and a hub of enteroendocrine and neuroactive signaling, these findings have direct relevance to the gut–brain axis. By shaping the flux of metabolites, neurotransmitter precursors, and immune signals that reach systemic circulation, the SI microbiome may influence neurological processes ranging from satiety and mood to visceral pain. Thus, our work underscores that interventions targeting SI dysbiosis are not only critical for gut health but may also provide new opportunities to modulate brain function and behavior.

Qiufu Ma

(he/him)

Chair Professor of Neurobiology

Director of the Research Center for Systems Physiology and Bioelectronic Medicine

Westlake University

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Modulation of inflammation and pain by electroacupuncture

Acupuncture at specific body regions can distantly modulate body physiology, partly operating through somatosensory-autonomic reflexes. For example, we and others found that low-intensity electroacupuncture (EA) at limb-region acupoints, such as "Zusanli", could drive a unique autonomic pathway that can suppress systemic inflammation induced by bacterial endotoxins. We then identified a group of sensory neurons necessary for EA to drive this anti-inflammatory axis. Based on the projections of these sensory nerves to tissues, we can predict effective and non-effective body regions. Most recently, we found that high-intensity EA can attenuate post-surgery pain, by driving a different somatosensory-autonomic pathway. These findings offer neuroanatomical support for EA to modulate inflammation and pain.

Kara Margolis

(she/her)

Professor of Molecular Pathobiology, Cell Biology and Pediatrics

New York University

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Afferent serotonergic signaling in gut–brain health: Clinical implications for mood and abdominal pain

There is a continuous bidirectional communication between the gut and the brain that serves to modulate many aspects of gut and brain health. It has been increasingly recognized that alterations in the gut ecosystem may impact what are traditionally recognized as brain disorders ,including mood dysfunction and pain. A key modulator in both mood and pain is serotonin. This talk will include highlights of the classic and recently recognized roles of intestinal serotnin in mood and pain.

Christoph Thaiss

(he/him)

Assistant Professor of Pathology

Arc Institute, Stanford University

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Body-brain interactions: a new frontier in biomedicine

Many common human diseases, including obesity and diabetes, neurodegenerative diseases, chronic inflammatory diseases, and cancer, are strongly shaped by lifestyle and environmental influences. The molecular pathways by which environmental factors shape our propensity for these diseases, however, remain poorly understood. We have recently discovered several mechanisms of body-brain communication that mediate the impact of lifestyle elements on host physiology. Identifying the interoceptive pathways that are involved in the control of host physiology and in the molecular etiology of human disease holds great potential for the discovery of new treatment approaches.