Nearly 1 in 5 individuals in the U.S. suffers from a mental disorder, yet the underlying causes for many psychiatric illnesses are largely unknown, and effective treatments are lacking. Recent preclinical studies have revealed striking effects of microbiome manipulations on complex, higher-order behaviors, including anxiety, sociability, cognition and emotional behavior. Moreover, molecular assessments reveal a key role for the microbiome in modulating neurochemical metabolism, global brain gene expression, microglial activation and blood brain barrier permeability. Driven by these findings, recent examination of patients suffering from mental disorders, including schizophrenia and depression, reveals dysbiosis of the microbiota. Altogether, these findings raise the interesting prospect of whether changes in the microbiome can contribute to, or be used to modify, symptoms of brain and behavioral disorders.
 

Current Research Projects

The laboratory of Dr. Elaine Hsiao at UCLA is studying microbiome-gut-brain effects on symptoms of neurodevelopmental disorders and molecular signaling between gut microbes and the nervous system. Dr. Hsiao’s previous work in this area demonstrated that postnatal modification of the commensal microbiota improves GI and behavioral symptoms in mouse models of genetic and environmental risk factors for autism. This work is the first to demonstrate that the microbiota regulates stereotypic, sensorimotor and communicative behavior, and to further reveal that microbe-mediated changes in levels of neuroactive metabolites impact behavior. A separate study conducted by the Hsiao lab identified a particular bacterial consortium from the human and mouse microbiome that reversibly modulates host serotonin biosynthesis and ameliorates serotonin-related disease phenotypes in mice. The group is following up on both these areas, studying how gene-environment interactions involving the microbiota affect disorders, like epilepsy and autism, and how microbes influence neurochemical levels and neuronal activation.

Representative Publications:

  • Yano JM, Yu K, Donaldson G, Shastri G, Ma L, Ann P, Nagler C, Ismagilov RF, Mazmanian SK, Hsiao EY (2015) Indigenous bacteria from the gut microbiota regulate host serotonin biosynthesis. Cell, 161:264-76.
  • Hsiao EY, McBride SW, Hsien S, Sharon G, Hyde ER, McCue T, Codelli JA, Chow J, Reisman SE, Petrosino JF, Patterson PH*, Mazmanian SK* (2013) The microbiota modulates behavioral and physiological abnormalities associated with neurodevelopmental disorders. Cell, 155:1451-1463.
  • Hsiao EY, McBride SW, Chow J, Mazmanian SK, Patterson PH (2012) Modeling an autism risk factor in mice leads to permanent immune dysregulation. PNAS 109:12776-81

 

Key People

Photo of Elaine Y. Hsiao, PhD
Elaine Y. Hsiao, PhD
Assistant Professor, Department of Integrative Biology and Physiology, De Logi Chair in Biological Sciences, Division of Digestive Diseases, Department of Medicine, David Geffen School of Medicine at UCLA
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Website: Hsiao Lab

Dr. Elaine Y. Hsiao is an Assistant Professor in the Department of Integrative Biology & Physiology at UCLA, where she leads a laboratory studying fundamental interactions between the microbiome, brain and behavior, and their applications to neurological disorders. Her studies on the relationships between the microbiota, immune system and nervous system led her to discover that the microbiota can regulate behavioral, metabolic and gastrointestinal abnormalities relevant to autism spectrum disorder (ASD). Her work in this area, and on neuroimmune interactions in autism, has led to several honors, including the National Institutes of Health Director’s Early Independence Award, distinction as Forbes’ 30 Under 30 in Science and Healthcare, National Geographic’s Emerging Explorer Award and fellowships from the National Institute of Mental Health and Autism Speaks. Inspired by this interplay between the microbiota and nervous system, the Hsiao laboratory is mining the human microbiota for microbial modulators of host neuroactive molecules, investigating the impact of microbiota-immune system interactions on neurodevelopment and examining the microbiome as an interface between gene-environment interactions in neurological diseases.

Relevant Recent Publications

  1. Yano JM, Yu K, Donaldson G, Shastri G, Ma L, Ann P, Nagler C, Ismagilov RF, Mazmanian SK, Hsiao EY (2015) Indigenous bacteria from the gut microbiota regulate host serotonin biosynthesis. Cell, 161:264-76.
  2. Hsiao EY, McBride SW, Hsien S, Sharon G, Hyde ER, McCue T, Codelli JA, Chow J, Reisman SE, Petrosino JF, Patterson PH*, Mazmanian SK* (2013) The microbiota modulates behavioral and physiological abnormalities associated with neurodevelopmental disorders. Cell, 155:1451-1463.
  3. Hsiao EY, McBride SW, Chow J, Mazmanian SK, Patterson PH (2012) Modeling an autism risk factor in mice leads to permanent immune dysregulation. PNAS 109:12776-81

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Helen Lavretsky, MD
Professor in Residence, Psychiatry and Biobehavioral Sciences, David Geffen School of Medicine at UCLA
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Phone: (310) 794-4619

Dr. Helen Lavretsky is the Geriatric Psychiatrist at UCLA with research interests in treatment and prevention of mood and cognitive disorders of aging. Her studies have already shown that mind-body exercise such as yoga and Tai Chi can help to reduce depression and cognitive decline in aging adults and in stressed caregivers. Current research studies offer participation in Tai Chi and yoga studies, as well as pharmacological studies for geriatric depression and mild cognitive impairment.

Dr. Lavretsky aims to investigate the role of microbiota in late life mood and cognitive disorders by comparing microbiome composition in those with and without mood and cognitive symptoms, and to develop interventions targeting microbiota and wellness for prevention of mood disorders and cognitive decline in older adults.

Relevant Recent Publications

  1. Lee S.M., Lavretsky H. “Microbiota and disorders of aging” IN: Complementary and Integrative Therapies for Mental Health and Aging. Eds: Lavretsky, Sajatovic, Reynolds, Oxford University Press [in press].

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