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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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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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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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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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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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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
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Description

High proportions of autistic children suffer from gastrointestinal (GI) disorders, implying a link between autism and abnormalities in gut microbial functions. Increasing evidence from recent high-throughput sequencing analyses indicates that disturbances in composition and diversity of gut microbiome are associated with various disease conditions. However, microbiome-level studies on autism are

High proportions of autistic children suffer from gastrointestinal (GI) disorders, implying a link between autism and abnormalities in gut microbial functions. Increasing evidence from recent high-throughput sequencing analyses indicates that disturbances in composition and diversity of gut microbiome are associated with various disease conditions. However, microbiome-level studies on autism are limited and mostly focused on pathogenic bacteria. Therefore, here we aimed to define systemic changes in gut microbiome associated with autism and autism-related GI problems. We recruited 20 neurotypical and 20 autistic children accompanied by a survey of both autistic severity and GI symptoms. By pyrosequencing the V2/V3 regions in bacterial 16S rDNA from fecal DNA samples, we compared gut microbiomes of GI symptom-free neurotypical children with those of autistic children mostly presenting GI symptoms. Unexpectedly, the presence of autistic symptoms, rather than the severity of GI symptoms, was associated with less diverse gut microbiomes. Further, rigorous statistical tests with multiple testing corrections showed significantly lower abundances of the genera Prevotella, Coprococcus, and unclassified Veillonellaceae in autistic samples. These are intriguingly versatile carbohydrate-degrading and/or fermenting bacteria, suggesting a potential influence of unusual diet patterns observed in autistic children. However, multivariate analyses showed that autism-related changes in both overall diversity and individual genus abundances were correlated with the presence of autistic symptoms but not with their diet patterns. Taken together, autism and accompanying GI symptoms were characterized by distinct and less diverse gut microbial compositions with lower levels of Prevotella, Coprococcus, and unclassified Veillonellaceae.

ContributorsKang, Dae Wook (Author) / Park, Jin (Author) / Ilhan, Zehra (Author) / Wallstrom, Garrick (Author) / LaBaer, Joshua (Author) / Adams, James (Author) / Krajmalnik-Brown, Rosa (Author) / Biodesign Institute (Contributor)
Created2013-06-03
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The impact of undergraduate research experiences (UREs) is supported by evidence from physical and life science fields, especially when student-apprentices work in traditional laboratories. Within social sciences specifically, some excellent student outcomes associated with UREs adhere to non–lab-based modalities like course-based research experiences (CUREs). Here, the authors evaluate the laboratory-based undergraduate research experiences (LUREs) as a potentially valuable

The impact of undergraduate research experiences (UREs) is supported by evidence from physical and life science fields, especially when student-apprentices work in traditional laboratories. Within social sciences specifically, some excellent student outcomes associated with UREs adhere to non–lab-based modalities like course-based research experiences (CUREs). Here, the authors evaluate the laboratory-based undergraduate research experiences (LUREs) as a potentially valuable approach for incorporating social science undergraduates in research. Using comparative analysis of survey data from students completing three types of social science-based UREs (n = 235), individual research experiences (IREs), CUREs, or LUREs, students perceived gains overall regardless of the type of experience, with some indication that LUREs are the most effective.

ContributorsRuth, Alissa (Author) / Brewis, Alexandra (Author) / Beresford, Melissa (Author) / Smith, Michael E. (Author) / Stojanowski, Christopher (Author) / Wutich, Amber (Author)
Created2023-11-13
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Background: Considering the distinct biological characteristics of Plasmodium species is crucial for control and elimination efforts, in particular when facing the spread of drug resistance. Whereas the evolutionary fitness of all malarial species could be approximated by the probability of being taken by a mosquito and then infecting a new host,

Background: Considering the distinct biological characteristics of Plasmodium species is crucial for control and elimination efforts, in particular when facing the spread of drug resistance. Whereas the evolutionary fitness of all malarial species could be approximated by the probability of being taken by a mosquito and then infecting a new host, the actual steps in the malaria life cycle leading to a successful transmission event show differences among Plasmodium species. These “steps” are called fitness components. Differences in terms of fitness components may affect how selection imposed by interventions, e.g. drug treatments, differentially acts on each Plasmodium species. Thus, a successful malaria control or elimination programme should understand how differences in fitness components among different malaria species could affect adaptive evolution (e.g. the emergence of drug resistance). In this investigation, the interactions between some fitness components and natural selection are explored.

Methods: A population-genetic model is formulated that qualitatively explains how different fitness components (in particular gametocytogenesis and longevity of gametocytes) affect selection acting on merozoites during the erythrocytic cycle. By comparing Plasmodium falciparum and Plasmodium vivax, the interplay of parasitaemia and gametocytaemia dynamics in determining fitness is modelled under circumstances that allow contrasting solely the differences between these two parasites in terms of their fitness components.

Results: By simulating fitness components, it is shown that selection acting on merozoites (e.g., on drug resistant mutations or malaria antigens) is more efficient in P. falciparum than in P. vivax. These results could explain, at least in part, why resistance against drugs, such as chloroquine (CQ) is highly prevalent in P. falciparum worldwide, while CQ is still a successful treatment for P. vivax despite its massive use. Furthermore, these analyses are used to explore the importance of understanding the dynamic of gametocytaemia to ascertain the spreading of drug resistance.

Conclusions: The strength of natural selection on mutations that express their advantage at the merozoite stage is different in P. vivax and P. falciparum. Species-specific differences in gametocytogenesis and longevity of gametocytes need to be accounted for when designing effective malaria control and elimination programmes. There is a need for reliable data on gametocytogenesis from field studies.

ContributorsSchneider, Kristan A. (Author) / Escalante, Ananias (Author) / Biodesign Institute (Contributor)
Created2013-01-11
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Lineage-committed cells of many tissues exhibit substantial plasticity in contexts such as wound healing and tumorigenesis, but the regulation of this process is not well understood. We identified the Hippo transducer WWTR1/TAZ in a screen of transcription factors that are able to prompt lineage switching of mammary epithelial cells. Forced

Lineage-committed cells of many tissues exhibit substantial plasticity in contexts such as wound healing and tumorigenesis, but the regulation of this process is not well understood. We identified the Hippo transducer WWTR1/TAZ in a screen of transcription factors that are able to prompt lineage switching of mammary epithelial cells. Forced expression of TAZ in luminal cells induces them to adopt basal characteristics, and depletion of TAZ in basal and/or myoepithelial cells leads to luminal differentiation. In human and mouse tissues, TAZ is active only in basal cells and is critical for basal cell maintenance during homeostasis. Accordingly, loss of TAZ affects mammary gland development, leading to an imbalance of luminal and basal populations as well as branching defects. Mechanistically, TAZ interacts with components of the SWI/SNF complex to modulate lineage-specific gene expression. Collectively, these findings uncover a new role for Hippo signaling in the determination of lineage identity through recruitment of chromatin-remodeling complexes.

ContributorsSkibinski, Adam (Author) / Breindel, Jerrica L. (Author) / Prat, Aleix (Author) / Galvan, Patricia (Author) / Smith, Elizabeth (Author) / Rolfs, Andreas (Author) / Gupta, Piyush B. (Author) / LaBaer, Joshua (Author) / Kuperwasser, Charlotte (Author) / Biodesign Institute (Contributor)
Created2014-03-27