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Open Access Publications from the University of California

Scholarly Works (120 results)

  • Thesis
  • Peer Reviewed
UCLA Electronic Theses and Dissertations (2016)

Obesity is a growing problem both in The United States and world-wide and women in The United States have the highest mean body mass index (BMI) of high-income countries. Brain imaging studies have provided great insights in the interplay between the gut and the brain in regulation of human ingestive behavior, allowing for the exploration of complex signaling in the brain related to appetite-stimulating cues. Obesity has been viewed as a disruption of the balance between homeostatic processing for energy needs and hedonic processing involved in the rewarding value of food, but these brain differences have yet to be fully examined when it comes to the brain’s resting state.

The primary aims of this dissertation were to explore the differences in homeostatic and hedonic brain networks in obese women using resting state techniques to compare frequency oscillations and functional connectivity with lean women at a baseline state and then to determine if functional connectivity would be altered by a variant of a known satiety hormone, GLP-1. In additional, to compare these brain abnormalities with behavioral measures related to appetite. This dissertation also includes a preliminary study examining the impact of high and low calorie beverages on hedonic and homeostatic networks of lean vs obese women while viewing pictures of food which pointed to key abnormalities of the obese woman’s brain and an obese-only discrepancy between brain activations and behavioral measures related to subjective feelings of fullness and appetite.

Our analyses at baseline indicated differences in hedonic regions for overweight and obese women, centering around a key region of reward, the nucleus accumbens which was shown to have an increase in grey matter volume as well as altered frequency distributions in the higher BMI group. Functional connectivity of the nucleus accumbens with other regions in the hedonic network was observed to be greater in the more obese group, a brain pattern also observed in many forms of addiction. Upon injection of the GLP-1 analog, Exenatide, functional connectivity was observed to increase more so in the obese group between key homeostatic regions centered around the Nucleus Tractus Solitaries (NTS). This drug-induced increase in functional connectivity was correlated with an increase of hunger in all subjects but more so in the obese. These results support the notion that Exenatide has an impact on brain connectivity, particularly in the obese and suggest the drug’s influence on appetite control might be linked to modified connectivity of an NTS-based network.

    Cover page: The Impact of GLP-1 Analog, Exenatide, on The Resting Brain of Lean vs Obese Women
    • Article
    • Peer Reviewed
    UCLA Previously Published Works (2024)
    The complex, bidirectional interactions between the brain, the gut, and the gut microbes are best referred to as the brain gut microbiome system. Animal and clinical studies have identified specific signaling mechanisms within this system, with gut microbes communicating to the brain through neuronal, endocrine, and immune pathways. The brain, in turn, modulates the composition and function of the gut microbiota through the autonomic nervous system, regulating gut motility, secretion, permeability, and the release of hormones impacting microbial gene expression. Perturbations at any level of these interactions can disrupt the intricate balance, potentially contributing to the pathogenesis of intestinal, metabolic, neurologic, and psychiatric disorders. Understanding these interactions and their underlying mechanisms holds promise for identifying biomarkers, as well as novel therapeutic targets, and for developing more effective treatment strategies for these complex disorders. Continued research will advance our knowledge of this system, with the potential for improved understanding and management of a wide range of disorders. This review provides an update on the current state of knowledge regarding this system, with a focus on recent advancements and emerging research areas.
      Cover page: Advances in Brain-Gut-Microbiome Interactions: A Comprehensive Update on Signaling Mechanisms, Disorders, and Therapeutic Implications.
      • Thesis
      • Peer Reviewed
      UCLA Electronic Theses and Dissertations (2015)

      Irritable Bowel Syndrome (IBS) is the most common chronic visceral pain syndrome characterized by chronic abdominal pain/discomfort associated with altered bowel habits. Cognitive, affective and psychosocial factors such as hypervigilance, hypersensitivity and selective attention of visceral pain are commonly seen in IBS patients. Many studies have demonstrated IBS-related biological alterations in the immune system, gut microbiota, gene polymorphisms and hypothalamic-pituitary-adrenal system. However, these findings are not able to explain the subjective pain experience of IBS patients. By applying different brain imaging technology (e.g. Magnetic Resonance Imaging [MRI]) in pain research, multiple brain regions involved in emotional arousal, reward, attentional and cognitive processes have been identified during the past decade. Based on the extensive epidemiological, psychophysiological and neurobiological information about pain mechanisms, there is a growing consensus that the central nervous system plays an important role in the pathophysiology of IBS symptoms, in addition to multiple other peripheral factors.

      This dissertation aims to identify IBS-related structural and functional brain signatures, and to integrate these signatures and clinical characteristics into a comprehensive disease model, which takes sex-related differences into account. The following analysis approaches were used to accomplish these aims: 1. Fractional amplitude of low frequency fluctuation was applied to measure the power spectrum intensity of spontaneous brain oscillations during task-free resting-state functional MRI. 2. Functional connectivity analysis was performed to examine how different parts of the brain work together and to identify dysfunction of the communication in the disease group. 3. Task-based functional MRI study approach was used to study how brain responses to certain stimuli differ between individuals with IBS and healthy controls. In addition, to determine the disease specificity of observed brain networks, brain structural changes were compared between IBS patients and patients with inflammatory bowel diseases. Altogether, with different aspects of research approaches to investigate IBS, progress has been made to better understand the pathophysiology of the disorder.

        Cover page: Structural and Functional Brain Alterations in Patients with Irritable Bowel Syndrome
        • Article
        • Peer Reviewed
        UCLA Previously Published Works (2014)
        Alterations in the bidirectional interactions between the intestine and the nervous system have important roles in the pathogenesis of irritable bowel syndrome (IBS). A body of largely preclinical evidence suggests that the gut microbiota can modulate these interactions. A small and poorly defined role for dysbiosis in the development of IBS symptoms has been established through characterization of altered intestinal microbiota in IBS patients and reported improvement of subjective symptoms after its manipulation with prebiotics, probiotics, or antibiotics. It remains to be determined whether IBS symptoms are caused by alterations in brain signaling from the intestine to the microbiota or primary disruption of the microbiota, and whether they are involved in altered interactions between the brain and intestine during development. We review the potential mechanisms involved in the pathogenesis of IBS in different groups of patients. Studies are needed to better characterize alterations to the intestinal microbiome in large cohorts of well-phenotyped patients, and to correlate intestinal metabolites with specific abnormalities in gut-brain interactions.
          Cover page: Brain–Gut Microbiome Interactions and Functional Bowel Disorders
          • Article
          • Peer Reviewed
          UCLA Previously Published Works (2020)
          Normal eating behaviour is coordinated by the tightly regulated balance between intestinal and extra-intestinal homeostatic and hedonic mechanisms. By contrast, food addiction is a complex, maladaptive eating behaviour that reflects alterations in brain-gut-microbiome (BGM) interactions and a shift of this balance towards hedonic mechanisms. Each component of the BGM axis has been implicated in the development of food addiction, with both brain to gut and gut to brain signalling playing a role. Early-life influences can prime the infant gut microbiome and brain for food addiction, which might be further reinforced by increased antibiotic usage and dietary patterns throughout adulthood. The ubiquitous availability and marketing of inexpensive, highly palatable and calorie-dense food can further shift this balance towards hedonic eating through both central (disruptions in dopaminergic signalling) and intestinal (vagal afferent function, metabolic endotoxaemia, systemic immune activation, changes to gut microbiome and metabolome) mechanisms. In this Review, we propose a systems biology model of BGM interactions, which incorporates published reports on food addiction, and provides novel insights into treatment targets aimed at each level of the BGM axis.
            Cover page: Brain–gut–microbiome interactions in obesity and food addiction
            • Article
            • Peer Reviewed
            UCLA Previously Published Works (2015)
            Tremendous progress has been made in characterizing the bidirectional interactions between the central nervous system, the enteric nervous system, and the gastrointestinal tract. A series of provocative preclinical studies have suggested a prominent role for the gut microbiota in these gut-brain interactions. Based on studies using rodents raised in a germ-free environment, the gut microbiota appears to influence the development of emotional behavior, stress- and pain-modulation systems, and brain neurotransmitter systems. Additionally, microbiota perturbations by probiotics and antibiotics exert modulatory effects on some of these measures in adult animals. Current evidence suggests that multiple mechanisms, including endocrine and neurocrine pathways, may be involved in gut microbiota-to-brain signaling and that the brain can in turn alter microbial composition and behavior via the autonomic nervous system. Limited information is available on how these findings may translate to healthy humans or to disease states involving the brain or the gut/brain axis. Future research needs to focus on confirming that the rodent findings are translatable to human physiology and to diseases such as irritable bowel syndrome, autism, anxiety, depression, and Parkinson's disease.
              Cover page: Gut/brain axis and the microbiota
              • Article
              • Peer Reviewed
              UCLA Previously Published Works (2004)
              The so-called functional somatic syndromes comprise a group of disorders that are primarily symptom-based, multisystemic in presentation and probably involve alterations in mind-brain-body interactions. The emerging neurobiological models of allostasis/allostatic load and of the emotional motor system show striking similarities with concepts used by Traditional Chinese Medicine (TCM) to understand the functional somatic disorders and their underlying pathogenesis. These models incorporate a macroscopic perspective, accounting for the toll of acute and chronic traumas, physical and emotional stressors and the complex interactions between the mind, brain and body. The convergence of these biomedical models with the ancient paradigm of TCM may provide a new insight into scientifically verifiable diagnostic and therapeutic approaches for these common disorders.
                Cover page: Functional Somatic Syndromes: Emerging Biomedical Models and Traditional Chinese Medicine
                • Article
                • Peer Reviewed
                UCLA Previously Published Works (2019)

                Background & aims

                Based largely on results from preclinical studies, the concept of a brain gut microbiome axis has been established, mediating bidirectional communication between the gut, its microbiome, and the nervous system. Limited data obtained in human beings suggest that alterations in these interactions may play a role in several brain gut disorders.

                Methods

                We reviewed the preclinical and clinical literature related to the topic of brain gut microbiome interactions.

                Results

                Well-characterized bidirectional communication channels, involving neural, endocrine, and inflammatory mechanisms, exist between the gut and the brain. Communication through these channels may be modulated by variations in the permeability of the intestinal wall and the blood-brain barrier. Brain gut microbiome interactions are programmed during the first 3 years of life, including the prenatal period, but can be modulated by diet, medications, and stress throughout life. Based on correlational studies, alterations in these interactions have been implicated in the regulation of food intake, obesity, and in irritable bowel syndrome, even though causality remains to be established.

                Conclusions

                Targets within the brain gut microbiome axis have the potential to become targets for novel drug development for brain gut disorders.
                  Cover page: The Gut–Brain Axis and the Microbiome: Mechanisms and Clinical Implications
                  • Article
                  • Peer Reviewed
                  UCLA Previously Published Works (2020)

                  Purpose of review

                  Focusing on studies published within the last decade, we review the literature on the seminal microbiome and male factor infertility. We highlight potential mechanisms by which microbes may impact fertility and underscore key limitations and clinical implications of these studies.

                  Recent findings

                  The seminal microbiome encompasses a metabolically and phylogenetically diverse group of microorganisms. Lactobacillus was consistently associated with normal semen analysis parameters and fertility; Anaerococcus was negatively associated with semen quality. These microbes may participate in a complex cross-talk with the host immune system, thereby modulating local and perhaps systemic inflammatory responses, impacting semen quality.

                  Summary

                  Research investigating the intersection between the seminal microbiome and male fertility is still in its infancy. Recent investigations have been exclusively cross-sectional, correlational studies, limiting the clinical applicability of published research. Prospective studies with more sophisticated methodologies are necessary.
                    Cover page: The Seminal Microbiome and Male Factor Infertility
                    • Article
                    • Peer Reviewed
                    UC Berkeley Previously Published Works (2014)
                      Cover page: Gastrointestinal dysbiosis.
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