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Recent studies suggest a role for the microbiota in autism spectrum disorders (ASD), potentially arising from their role in modulating the immune system and gastrointestinal (GI) function or from gut–brain interactions dependent or independent from the immune system. GI problems such as chronic constipation and/or diarrhea are common in children

Recent studies suggest a role for the microbiota in autism spectrum disorders (ASD), potentially arising from their role in modulating the immune system and gastrointestinal (GI) function or from gut–brain interactions dependent or independent from the immune system. GI problems such as chronic constipation and/or diarrhea are common in children with ASD, and significantly worsen their behavior and their quality of life. Here we first summarize previously published data supporting that GI dysfunction is common in individuals with ASD and the role of the microbiota in ASD. Second, by comparing with other publically available microbiome datasets, we provide some evidence that the shifted microbiota can be a result of westernization and that this shift could also be framing an altered immune system. Third, we explore the possibility that gut–brain interactions could also be a direct result of microbially produced metabolites.

ContributorsKrajmalnik-Brown, Rosa (Author) / Lozupone, Catherine (Author) / Kang, Dae Wook (Author) / Adams, James (Author) / Biodesign Institute (Contributor)
Created2015-03-12
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Description

There is a growing body of scientific evidence that the health of the microbiome (the trillions of microbes that inhabit the human host) plays an important role in maintaining the health of the host and that disruptions in the microbiome may play a role in certain disease processes. An increasing

There is a growing body of scientific evidence that the health of the microbiome (the trillions of microbes that inhabit the human host) plays an important role in maintaining the health of the host and that disruptions in the microbiome may play a role in certain disease processes. An increasing number of research studies have provided evidence that the composition of the gut (enteric) microbiome (GM) in at least a subset of individuals with autism spectrum disorder (ASD) deviates from what is usually observed in typically developing individuals. There are several lines of research that suggest that specific changes in the GM could be causative or highly associated with driving core and associated ASD symptoms, pathology, and comorbidities which include gastrointestinal symptoms, although it is also a possibility that these changes, in whole or in part, could be a consequence of underlying pathophysiological features associated with ASD. However, if the GM truly plays a causative role in ASD, then the manipulation of the GM could potentially be leveraged as a therapeutic approach to improve ASD symptoms and/or comorbidities, including gastrointestinal symptoms.

One approach to investigating this possibility in greater detail includes a highly controlled clinical trial in which the GM is systematically manipulated to determine its significance in individuals with ASD. To outline the important issues that would be required to design such a study, a group of clinicians, research scientists, and parents of children with ASD participated in an interdisciplinary daylong workshop as an extension of the 1st International Symposium on the Microbiome in Health and Disease with a Special Focus on Autism (www.microbiome-autism.com). The group considered several aspects of designing clinical studies, including clinical trial design, treatments that could potentially be used in a clinical trial, appropriate ASD participants for the clinical trial, behavioral and cognitive assessments, important biomarkers, safety concerns, and ethical considerations. Overall, the group not only felt that this was a promising area of research for the ASD population and a promising avenue for potential treatment but also felt that further basic and translational research was needed to clarify the clinical utility of such treatments and to elucidate possible mechanisms responsible for a clinical response, so that new treatments and approaches may be discovered and/or fostered in the future.

ContributorsFrye, Richard E. (Author) / Slattery, John (Author) / MacFabe, Derrick F. (Author) / Allen-Vercoe, Emma (Author) / Parker, William (Author) / Rodakis, John (Author) / Adams, James (Author) / Krajmalnik-Brown, Rosa (Author) / Bolte, Ellen (Author) / Kahler, Stephen (Author) / Jennings, Jana (Author) / James, Jill (Author) / Cerniglia, Carl E. (Author) / Midtvedt, Tore (Author) / Ira A. Fulton Schools of Engineering (Contributor)
Created2015-05-07
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Description

Critical flicker fusion thresholds (CFFTs) describe when quick amplitude modulations of a light source become undetectable as the frequency of the modulation increases and are thought to underlie a number of visual processing skills, including reading. Here, we compare the impact of two vision-training approaches, one involving contrast sensitivity training

Critical flicker fusion thresholds (CFFTs) describe when quick amplitude modulations of a light source become undetectable as the frequency of the modulation increases and are thought to underlie a number of visual processing skills, including reading. Here, we compare the impact of two vision-training approaches, one involving contrast sensitivity training and the other directional dot-motion training, compared to an active control group trained on Sudoku. The three training paradigms were compared on their effectiveness for altering CFFT. Directional dot-motion and contrast sensitivity training resulted in significant improvement in CFFT, while the Sudoku group did not yield significant improvement. This finding indicates that dot-motion and contrast sensitivity training similarly transfer to effect changes in CFFT. The results, combined with prior research linking CFFT to high-order cognitive processes such as reading ability, and studies showing positive impact of both dot-motion and contrast sensitivity training in reading, provide a possible mechanistic link of how these different training approaches impact reading abilities.

ContributorsZhou, Tianyou (Author) / Nanez, Jose (Author) / Zimmerman, Daniel (Author) / Holloway, Steven (Author) / Seitz, Aaron (Author) / New College of Interdisciplinary Arts and Sciences (Contributor)
Created2016-10-26
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Description

Although autism spectrum disorder (ASD) is a serious lifelong condition, its underlying neural mechanism remains unclear. Recently, neuroimaging-based classifiers for ASD and typically developed (TD) individuals were developed to identify the abnormality of functional connections (FCs). Due to over-fitting and interferential effects of varying measurement conditions and demographic distributions, no

Although autism spectrum disorder (ASD) is a serious lifelong condition, its underlying neural mechanism remains unclear. Recently, neuroimaging-based classifiers for ASD and typically developed (TD) individuals were developed to identify the abnormality of functional connections (FCs). Due to over-fitting and interferential effects of varying measurement conditions and demographic distributions, no classifiers have been strictly validated for independent cohorts. Here we overcome these difficulties by developing a novel machine-learning algorithm that identifies a small number of FCs that separates ASD versus TD. The classifier achieves high accuracy for a Japanese discovery cohort and demonstrates a remarkable degree of generalization for two independent validation cohorts in the USA and Japan. The developed ASD classifier does not distinguish individuals with major depressive disorder and attention-deficit hyperactivity disorder from their controls but moderately distinguishes patients with schizophrenia from their controls. The results leave open the viable possibility of exploring neuroimaging-based dimensions quantifying the multiple-disorder spectrum.

ContributorsYahata, Noriaki (Author) / Morimoto, Jun (Author) / Hashimoto, Ryuichiro (Author) / Lisi, Giuseppe (Author) / Shibata, Kazuhisa (Author) / Kawakubo, Yuki (Author) / Kuwabara, Hitoshi (Author) / Kuroda, Miho (Author) / Yamada, Takashi (Author) / Megumi, Fukuda (Author) / Imamizu, Hiroshi (Author) / Nanez, Jose (Author) / Takahashi, Hidehiko (Author) / Okamoto, Yasumasa (Author) / Kasai, Kiyoto (Author) / Kato, Nobumasa (Author) / Sasaki, Yuka (Author) / Watanabe, Takeo (Author) / Kawato, Mitsuo (Author) / New College of Interdisciplinary Arts and Sciences (Contributor)
Created2016-04-14
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Description

In this study, we examine how development status and water scarcity shape people's perceptions of "hard path" and "soft path" water solutions. Based on ethnographic research conducted in four semi-rural/peri-urban sites (in Bolivia, Fiji, New Zealand, and the US), we use content analysis to conduct statistical and thematic comparisons of

In this study, we examine how development status and water scarcity shape people's perceptions of "hard path" and "soft path" water solutions. Based on ethnographic research conducted in four semi-rural/peri-urban sites (in Bolivia, Fiji, New Zealand, and the US), we use content analysis to conduct statistical and thematic comparisons of interview data. Our results indicate clear differences associated with development status and, to a lesser extent, water scarcity. People in the two less developed sites were more likely to suggest hard path solutions, less likely to suggest soft path solutions, and more likely to see no path to solutions than people in the more developed sites. Thematically, people in the two less developed sites envisioned solutions that involve small-scale water infrastructure and decentralized, community-based solutions, while people in the more developed sites envisioned solutions that involve large-scale infrastructure and centralized, regulatory water solutions. People in the two water-scarce sites were less likely to suggest soft path solutions and more likely to see no path to solutions (but no more likely to suggest hard path solutions) than people in the water-rich sites. Thematically, people in the two water-rich sites seemed to perceive a wider array of unrealized potential soft path solutions than those in the water-scarce sites. On balance, our findings are encouraging in that they indicate that people are receptive to soft path solutions in a range of sites, even those with limited financial or water resources. Our research points to the need for more studies that investigate the social feasibility of soft path water solutions, particularly in sites with significant financial and natural resource constraints.

ContributorsWutich, Amber (Author) / White, A. C. (Author) / White, Dave (Author) / Larson, Kelli (Author) / Brewis Slade, Alexandra (Author) / Roberts, Christine (Author) / College of Liberal Arts and Sciences (Contributor)
Created2014-01-13
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Description

Background: Weight-related stigma is reported frequently by higher body-weight patients in healthcare settings. Bariatric surgery triggers profound weight loss. This weight loss may therefore alleviate patients' experiences of weight-related stigma within healthcare settings. In non-clinical settings, weight-related stigma is associated with weight-inducing eating patterns. Dietary adherence is a major challenge

Background: Weight-related stigma is reported frequently by higher body-weight patients in healthcare settings. Bariatric surgery triggers profound weight loss. This weight loss may therefore alleviate patients' experiences of weight-related stigma within healthcare settings. In non-clinical settings, weight-related stigma is associated with weight-inducing eating patterns. Dietary adherence is a major challenge after bariatric surgery.

Objectives: (1) Evaluate the relationship between weight-related stigma and post-surgical dietary adherence; (2) understand if weight loss reduces weight-related stigma, thereby improving post-surgical dietary adherence; and (3) explore provider and patient perspectives on adherence and stigma in healthcare settings.

Design: This mixed methods study contrasts survey responses from 300 postoperative bariatric patients with ethnographic data based on interviews with 35 patients and extensive multi-year participant-observation within a clinic setting. The survey measured experiences of weight-related stigma, including from healthcare professionals, on the Interpersonal Sources of Weight Stigma scale and internalized stigma based on the Weight Bias Internalization Scale. Dietary adherence measures included patient self-reports, non-disordered eating patterns reported on the Disordered Eating after Bariatric Surgery scale, and food frequencies. Regression was used to assess the relationships among post-surgical stigma, dietary adherence, and weight loss. Qualitative analyses consisted of thematic analysis.

Results: The quantitative data show that internalized stigma and general experiences of weight-related stigma predict worse dietary adherence, even after weight is lost. The qualitative data show patients did not generally recognize this connection, and health professionals explained it as poor patient compliance.
Conclusion: Reducing perceptions of weight-related stigma in healthcare settings and weight bias internalization could enhance dietary adherence, regardless of time since patient's weight-loss surgery.

ContributorsRaves, Danielle (Author) / Brewis Slade, Alexandra (Author) / Trainer, Sarah (Author) / Han, Seung-Yong (Author) / Wutich, Amber (Author) / College of Liberal Arts and Sciences (Contributor)
Created2016-10-10
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Description

Visual perceptual learning (VPL) is defined as visual performance improvement after visual experiences. VPL is often highly specific for a visual feature presented during training. Such specificity is observed in behavioral tuning function changes with the highest improvement centered on the trained feature and was originally thought to be evidence

Visual perceptual learning (VPL) is defined as visual performance improvement after visual experiences. VPL is often highly specific for a visual feature presented during training. Such specificity is observed in behavioral tuning function changes with the highest improvement centered on the trained feature and was originally thought to be evidence for changes in the early visual system associated with VPL. However, results of neurophysiological studies have been highly controversial concerning whether the plasticity underlying VPL occurs within the visual cortex. The controversy may be partially due to the lack of observation of neural tuning function changes in multiple visual areas in association with VPL. Here using human subjects we systematically compared behavioral tuning function changes after global motion detection training with decoded tuning function changes for 8 visual areas using pattern classification analysis on functional magnetic resonance imaging (fMRI) signals. We found that the behavioral tuning function changes were extremely highly correlated to decoded tuning function changes only in V3A, which is known to be highly responsive to global motion with human subjects. We conclude that VPL of a global motion detection task involves plasticity in a specific visual cortical area.

ContributorsShibata, Kazuhisa (Author) / Chang, Li-Hung (Author) / Kim, Dongho (Author) / Nanez, Jose (Author) / Kamitani, Yukiyasu (Author) / Watanabe, Takeo (Author) / Sasaki, Yuka (Author) / New College of Interdisciplinary Arts and Sciences (Contributor)
Created2012-08-28
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Description

Background: Autism spectrum disorders (ASD) are complex neurobiological disorders that impair social interactions and communication and lead to restricted, repetitive, and stereotyped patterns of behavior, interests, and activities. The causes of these disorders remain poorly understood, but gut microbiota, the 1013 bacteria in the human intestines, have been implicated because children

Background: Autism spectrum disorders (ASD) are complex neurobiological disorders that impair social interactions and communication and lead to restricted, repetitive, and stereotyped patterns of behavior, interests, and activities. The causes of these disorders remain poorly understood, but gut microbiota, the 1013 bacteria in the human intestines, have been implicated because children with ASD often suffer gastrointestinal (GI) problems that correlate with ASD severity. Several previous studies have reported abnormal gut bacteria in children with ASD. The gut microbiome-ASD connection has been tested in a mouse model of ASD, where the microbiome was mechanistically linked to abnormal metabolites and behavior. Similarly, a study of children with ASD found that oral non-absorbable antibiotic treatment improved GI and ASD symptoms, albeit temporarily. Here, a small open-label clinical trial evaluated the impact of Microbiota Transfer Therapy (MTT) on gut microbiota composition and GI and ASD symptoms of 18 ASD-diagnosed children.

Results: MTT involved a 2-week antibiotic treatment, a bowel cleanse, and then an extended fecal microbiota transplant (FMT) using a high initial dose followed by daily and lower maintenance doses for 7–8 weeks. The Gastrointestinal Symptom Rating Scale revealed an approximately 80% reduction of GI symptoms at the end of treatment, including significant improvements in symptoms of constipation, diarrhea, indigestion, and abdominal pain. Improvements persisted 8 weeks after treatment. Similarly, clinical assessments showed that behavioral ASD symptoms improved significantly and remained improved 8 weeks after treatment ended. Bacterial and phage deep sequencing analyses revealed successful partial engraftment of donor microbiota and beneficial changes in the gut environment. Specifically, overall bacterial diversity and the abundance of Bifidobacterium, Prevotella, and Desulfovibrio among other taxa increased following MTT, and these changes persisted after treatment stopped (followed for 8 weeks).

Conclusions: This exploratory, extended-duration treatment protocol thus appears to be a promising approach to alter the gut microbiome and virome and improve GI and behavioral symptoms of ASD. Improvements in GI symptoms, ASD symptoms, and the microbiome all persisted for at least 8 weeks after treatment ended, suggesting a long-term impact.

ContributorsKang, Dae Wook (Author) / Adams, James (Author) / Gregory, Ann C. (Author) / Borody, Thomas (Author) / Chittick, Lauren (Author) / Fasano, Alessio (Author) / Khoruts, Alexander (Author) / Geis, Elizabeth (Author) / Maldonado Ortiz, Juan (Author) / McDonough-Means, Sharon (Author) / Pollard, Elena (Author) / Roux, Simon (Author) / Sadowsky, Michael J. (Author) / Schwarzberg Lipson, Karen (Author) / Sullivan, Matthew B. (Author) / Caporaso, J. Gregory (Author) / Krajmalnik-Brown, Rosa (Author) / Biodesign Institute (Contributor)
Created2017-01-23
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Description

Background: Multiple studies show that obesity and depression tend to cluster in women. An “appearance concern” pathway has been proposed as one basic explanation of why higher weights might lead to depression. The transition to motherhood is a life phase in which women’s body image, weight, and depressive risk are in

Background: Multiple studies show that obesity and depression tend to cluster in women. An “appearance concern” pathway has been proposed as one basic explanation of why higher weights might lead to depression. The transition to motherhood is a life phase in which women’s body image, weight, and depressive risk are in flux, with average weight increasing overall during this period. Examination of how these factors interact from pre- to post-pregnancy provides a means to test how body image plays a key role, as proposed, in causally shaping women’s depressive risk.

Methods: Tracking 39,915 pregnant women in the Norwegian Mother and Child (MoBA) Cohort Study forward 36 months after their deliveries, we test the moderating and mediating effects of body image concerns on the emergence of new mothers’ depressive symptoms by using a binary logistic regression model with a discrete-time event history approach and mediation analysis with bootstrapping.

Results: For women with high pre-pregnancy body mass index (BMI), weight gain heightens their depressive symptoms over time. Body image concerns mediate the association between weight gain and the development of depressive symptoms regardless of weight status. However, the mediation effect is more evident for women with higher pre-pregnancy BMI. Conversely, better body image is highly protective against the transition to mild or more severe depressive symptoms among new mothers, but only for women who were not classified as obese prior to their pregnancies.

Conclusions: These findings support a role for body image concerns in the etiology of depressive symptoms during the transition to motherhood. The findings suggest body image interventions before or during pregnancy could help reduce risks of depression in the early postpartum period and well beyond.

ContributorsHan, Seung-Yong (Author) / Brewis Slade, Alexandra (Author) / Wutich, Amber (Author) / College of Liberal Arts and Sciences (Contributor)
Created2016-07-29
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Description

Food and water shortages are two of the greatest challenges facing humans in the coming century. While our theoretical understanding of how humans become vulnerable to and cope with hunger is relatively well developed, anthropological research on parallel problems in the water domain is limited. By carefully considering well-established propositions

Food and water shortages are two of the greatest challenges facing humans in the coming century. While our theoretical understanding of how humans become vulnerable to and cope with hunger is relatively well developed, anthropological research on parallel problems in the water domain is limited. By carefully considering well-established propositions derived from the food literature against what is known about water, our goal in this essay is to advance identifying, theorizing, and testing a broader anthropology of resource insecurity. Our analysis focuses on (1) the causes of resource insecurity at the community level, (2) “coping” responses to resource insecurity at the household level, and (3) the effect of insecurity on emotional well-being and mental health at the individual level. Based on our findings, we argue that human experiences of food and water insecurity are sufficiently similar to facilitate a broader theory of resource insecurity, including in how households and individuals cope. There are also important differences between food and water insecurity, including the role of structural factors (such as markets) in creating community-level vulnerabilities. These suggest food and water insecurity may also produce household struggles and individual suffering along independent pathways.

ContributorsWutich, Amber (Author) / Brewis Slade, Alexandra (Author) / College of Liberal Arts and Sciences (Contributor)
Created2014-08-01