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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

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

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
Description

This paper considers the changes in education and capacity building that are needed in response to environmental and social challenges of the 21st Century. We argue that such changes will require more than adjustments in current educational systems, research funding strategies, and interdisciplinary collaborations. Instead, it calls for a deeper

This paper considers the changes in education and capacity building that are needed in response to environmental and social challenges of the 21st Century. We argue that such changes will require more than adjustments in current educational systems, research funding strategies, and interdisciplinary collaborations. Instead, it calls for a deeper questioning of the assumptions and beliefs that frame both problems and solutions. We first discuss the challenges of transforming education and capacity building within five key arenas: interdisciplinary research; university education systems; primary and secondary education systems; researchers from the developing world; and the public at large and politicians. Our starting point is that any type of revolution that is proposed in response to global change is likely to reflect the educational perspectives and paradigms of those calling for the revolution. We differentiate between a circular revolution (as in the "plan-do-check-act cycle" often used in change management) versus an axial revolution (moving to a different way of thinking about the issues), arguing that the latter is a more appropriate response to the complex transdisciplinary challenges posed by global environmental change. We present some potential tools to promote an axial revolution, and consider the limits to this approach. We conclude that rather than promoting one large and ideologically homogenous revolution in education and capacity building, there is a need for a revolution in the way that leaders working with education and capacity building look at systems and processes of change. From this perspective, transformative learning may not only be desirable, but critical in responding to the challenges posed by global environmental change.

ContributorsO'Brien, Karen (Author) / Reams, Jonathan (Author) / Caspari, Anne (Author) / Dugmore, Andrew (Author) / Faghihimani, Maryam (Author) / Fazey, Ioan (Author) / Hackmann, Heide (Author) / Manuel-Navarrete, David (Author) / Marks, John (Author) / Miller, Riel (Author) / Raivio, Kari (Author) / Romero-Lankao, Patricia (Author) / Virji, Hassan (Author) / Vogel, Coleen (Author) / Winiwarter, Verena (Author) / Julie Ann Wrigley Global Institute of Sustainability (Contributor)
Created2013-08-12
Description

Widespread contamination of groundwater by chlorinated ethenes and their biological dechlorination products necessitates the reliable monitoring of liquid matrices; current methods approved by the U.S. Environmental Protection Agency (EPA) require a minimum of 5 mL of sample volume and cannot simultaneously detect all transformative products. This paper reports on the

Widespread contamination of groundwater by chlorinated ethenes and their biological dechlorination products necessitates the reliable monitoring of liquid matrices; current methods approved by the U.S. Environmental Protection Agency (EPA) require a minimum of 5 mL of sample volume and cannot simultaneously detect all transformative products. This paper reports on the simultaneous detection of six chlorinated ethenes and ethene itself, using a liquid sample volume of 1 mL by concentrating the compounds onto an 85-µm carboxen-polydimenthylsiloxane solid-phase microextraction fiber in 5 min and subsequent chromatographic analysis in 9.15 min. Linear increases in signal response were obtained over three orders of magnitude (∼0.05 to ∼50 µM) for simultaneous analysis with coefficient of determination (R2) values of ≥ 0.99. The detection limits of the method (1.3–6 µg/L) were at or below the maximum contaminant levels specified by the EPA. Matrix spike studies with groundwater and mineral medium showed recovery rates between 79–108%. The utility of the method was demonstrated in lab-scale sediment flow-through columns assessing the bioremediation potential of chlorinated ethene-contaminated groundwater. Owing to its low sample volume requirements, good sensitivity and broad target analyte range, the method is suitable for routine compliance monitoring and is particularly attractive for interpreting the bench-scale feasibility studies that are commonly performed during the remedial design stage of groundwater cleanup projects.

ContributorsZiv-El, Michal (Author) / Kalinowski, Tomasz (Author) / Krajmalnik-Brown, Rosa (Author) / Halden, Rolf (Author) / Biodesign Institute (Contributor)
Created2014-02-01
Description

The effects of urbanization on ozone levels have been widely investigated over cities primarily located in temperate and/or humid regions. In this study, nested WRF-Chem simulations with a finest grid resolution of 1 km are conducted to investigate ozone concentrations O3 due to urbanization within cities in arid/semi-arid environments. First,

The effects of urbanization on ozone levels have been widely investigated over cities primarily located in temperate and/or humid regions. In this study, nested WRF-Chem simulations with a finest grid resolution of 1 km are conducted to investigate ozone concentrations O3 due to urbanization within cities in arid/semi-arid environments. First, a method based on a shape preserving Monotonic Cubic Interpolation (MCI) is developed and used to downscale anthropogenic emissions from the 4 km resolution 2005 National Emissions Inventory (NEI05) to the finest model resolution of 1 km. Using the rapidly expanding Phoenix metropolitan region as the area of focus, we demonstrate the proposed MCI method achieves ozone simulation results with appreciably improved correspondence to observations relative to the default interpolation method of the WRF-Chem system. Next, two additional sets of experiments are conducted, with the recommended MCI approach, to examine impacts of urbanization on ozone production: (1) the urban land cover is included (i.e., urbanization experiments) and, (2) the urban land cover is replaced with the region's native shrubland. Impacts due to the presence of the built environment on O3 are highly heterogeneous across the metropolitan area. Increased near surface O3 due to urbanization of 10–20 ppb is predominantly a nighttime phenomenon while simulated impacts during daytime are negligible. Urbanization narrows the daily O3 range (by virtue of increasing nighttime minima), an impact largely due to the region's urban heat island. Our results demonstrate the importance of the MCI method for accurate representation of the diurnal profile of ozone, and highlight its utility for high-resolution air quality simulations for urban areas.

ContributorsLi, Jialun (Author) / Georgescu, Matei (Author) / Hyde, Peter (Author) / Mahalov, Alex (Author) / Moustaoui, Mohamed (Author) / Julie Ann Wrigley Global Institute of Sustainability (Contributor)
Created2014-11-01
Description

Studies in both terrestrial and aquatic ecosystems have documented the potential importance of consumers on ecosystem-level nutrient dynamics. This is especially true when aggregations of organisms create biogeochemical hotspots through nutrient consumption, assimilation, and remineralization via excretion and egestion. Here, we focused on aggregations of humans in cities to examine

Studies in both terrestrial and aquatic ecosystems have documented the potential importance of consumers on ecosystem-level nutrient dynamics. This is especially true when aggregations of organisms create biogeochemical hotspots through nutrient consumption, assimilation, and remineralization via excretion and egestion. Here, we focused on aggregations of humans in cities to examine how diet and waste management interact to drive nitrogen- (N) and phosphorus- (P) fluxes into nutrient pollution, inert forms, and nutrient recycling. We constructed six diet patterns (five US-based and one developing nation) to examine N- and P-consumption and excretion, and explored their implications for human health. Next, we constructed six waste-management patterns (three US and three for developing nations) to model how decisions at household and city scales determine the eventual fates of N and P. When compared to the US Recommended Daily Intake, all US diet patterns exceeded N and P requirements. Other than the “enriched CO2 environment scenario” diet, the typical US omnivore had the greatest excess (37% N and 62% P). Notably, P from food additives could account for all of the excess P found in US omnivore and vegetarian diets. Across all waste-management approaches, a greater proportion of P was stored or recycled (0 to > 100% more P than N) and a greater proportion of N was released as effluent (20 to > 100% more N than P) resulting in pollution enriched with N and a recycling stream enriched with P. In developing nations, 60% of N and 50% of P from excreta entered the environment as pollution because of a lack of sanitation infrastructure. Our study demonstrates a novel addition to modeling sustainable scenarios for urban N- and P-budgets by linking human diets and waste management through socio-ecological systems.

Created2015-07-01
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n public planning processes for sustainable urban development, planners and experts often face the challenge of engaging a public that is not familiar with sustainability principles or does not subscribe to sustainability values. Although there are calls to build the public’s sustainability literacy through social learning, such efforts require sufficient

n public planning processes for sustainable urban development, planners and experts often face the challenge of engaging a public that is not familiar with sustainability principles or does not subscribe to sustainability values. Although there are calls to build the public’s sustainability literacy through social learning, such efforts require sufficient time and other resources that are not always available. Alternatively, public participation processes may be realigned with the sustainability literacy the participants possess, and their capacity can modestly be built during the engagement. Asking what tools might successfully align public participation with participants’ sustainability literacy, this article describes and evaluates a public participation process in Phoenix, Arizona, in which researchers, in collaboration with city planners, facilitated sustainability conversations as part of an urban development process. The tool employed for Visually Enhanced Sustainability Conversation (VESC) was specifically designed to better align public participation with stakeholders’ sustainability literacy. We tested and evaluated VESC through interviews with participants, city planners, and members of the research team, as well as an analysis of project reports. We found that the use of VESC successfully facilitated discussions on pertinent sustainability issues and embedded sustainability objectives into the project reports. We close with recommendations for strengthening tools like VESC for future public engagements.

ContributorsCohen, Matthew (Author) / Wiek, Arnim (Author) / Kay, Braden (Author) / Harlow, John (Author) / Julie Ann Wrigley Global Institute of Sustainability (Contributor)
Created2015-07-03
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Successful careers in sustainability are determined by positive real-world change towards sustainability. This success depends heavily on professional skills in effective and compassionate communication, collaborative teamwork, or impactful stakeholder engagement, among others. These professional skills extend beyond content knowledge and methodical expertise. Current sustainability programs do not sufficiently facilitate students’

Successful careers in sustainability are determined by positive real-world change towards sustainability. This success depends heavily on professional skills in effective and compassionate communication, collaborative teamwork, or impactful stakeholder engagement, among others. These professional skills extend beyond content knowledge and methodical expertise. Current sustainability programs do not sufficiently facilitate students’ acquisition of such skills. This article presents a brief summary of professional skills, synthesized from the literature, and why they are relevant for sustainability professionals. Second, it presents how these skills have been taught in an undergraduate course in sustainability at Arizona State University, USA. Third, it critically discusses the effectiveness and challenges of that exemplary course. Finally, the article concludes with outlining the lessons learned that should be incorporated into future course offerings.

Created2017-03-07