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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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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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In this synthesis, we hope to accomplish two things: 1) reflect on how the analysis of the new archaeological cases presented in this special feature adds to previous case studies by revisiting a set of propositions reported in a 2006 special feature, and 2) reflect on four main ideas that

In this synthesis, we hope to accomplish two things: 1) reflect on how the analysis of the new archaeological cases presented in this special feature adds to previous case studies by revisiting a set of propositions reported in a 2006 special feature, and 2) reflect on four main ideas that are more specific to the archaeological cases: i) societal choices are influenced by robustness–vulnerability trade-offs, ii) there is interplay between robustness–vulnerability trade-offs and robustness–performance trade-offs, iii) societies often get locked in to particular strategies, and iv) multiple positive feedbacks escalate the perceived cost of societal change. We then discuss whether these lock-in traps can be prevented or whether the risks associated with them can be mitigated. We conclude by highlighting how these long-term historical studies can help us to understand current society, societal practices, and the nexus between ecology and society.

ContributorsSchoon, Michael (Author) / Fabricius, Christo (Author) / Anderies, John (Author) / Nelson, Margaret (Author) / College of Liberal Arts and Sciences (Contributor)
Created2011
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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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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

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

It is known that in classical fluids turbulence typically occurs at high Reynolds numbers. But can turbulence occur at low Reynolds numbers? Here we investigate the transition to turbulence in the classic Taylor-Couette system in which the rotating fluids are manufactured ferrofluids with magnetized nanoparticles embedded in liquid carriers. We

It is known that in classical fluids turbulence typically occurs at high Reynolds numbers. But can turbulence occur at low Reynolds numbers? Here we investigate the transition to turbulence in the classic Taylor-Couette system in which the rotating fluids are manufactured ferrofluids with magnetized nanoparticles embedded in liquid carriers. We find that, in the presence of a magnetic field transverse to the symmetry axis of the system, turbulence can occur at Reynolds numbers that are at least one order of magnitude smaller than those in conventional fluids. This is established by extensive computational ferrohydrodynamics through a detailed investigation of transitions in the flow structure, and characterization of behaviors of physical quantities such as the energy, the wave number, and the angular momentum through the bifurcations. A finding is that, as the magnetic field is increased, onset of turbulence can be determined accurately and reliably. Our results imply that experimental investigation of turbulence may be feasible by using ferrofluids. Our study of transition to and evolution of turbulence in the Taylor-Couette ferrofluidic flow system provides insights into the challenging problem of turbulence control.

ContributorsAltmeyer, Sebastian (Author) / Do, Younghae (Author) / Lai, Ying-Cheng (Author) / Ira A. Fulton Schools of Engineering (Contributor)
Created2015-06-12
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In order to improve the efficiency of government spending, it is necessary for the decentralized irrigation management to gain support from local institutions. Efficient institutions take on several distinct configurations in different irrigation districts. In this research, we upgrade Tang’s (1992) framework focusing on incentives, to a framework that includes

In order to improve the efficiency of government spending, it is necessary for the decentralized irrigation management to gain support from local institutions. Efficient institutions take on several distinct configurations in different irrigation districts. In this research, we upgrade Tang’s (1992) framework focusing on incentives, to a framework that includes institutional incentives and coordination. Within the framework, we then classify 5 institutional variables: water pricing reform (P), government funding (F), coordination by administration (C), having formal monitors (M) and self-organized management (S). This article processes the data obtained through a field survey (2009–2011) in 20 of China’s southern counties, where they implement the “Small-scale Irrigation and Water Conservancy Key Counties Construction (Key Counties Construction)”, a national project supported by the central government. Next, it applies Data Envelopment Analysis (DEA) to measure the efficiency of government spending and uses Qualitative Comparative Analysis (QCA) to extract efficient institutional configurations. It concludes that there are generally three types of institutional configurations able to improve the efficiency of government spending, which are respectively: “government funding combined with coordination by administration”, “water pricing reform combined with self-organized management and coordination by administration or water pricing reform combined with self-organized management and government funding and formal monitors” and “self-organized management”. Among these, the second configuration is a mixed governance structure with multiple institutions coexisting, and this configuration occurs in the most efficient key counties. For that reason, it is viewed as the mainstream irrigation management approach, and we expect it to be the development trend in the future. Although Chinese irrigation policies are formalizing effective local institutions, they are still not sufficient. Future policies are needed to 1) promote institutions of government support for water laws in order to build stable expectations for both water user associations (WUAs) and farmers, 2) guide water pricing reform by ensuring farmers’ water rights and regulating water markets, and 3) provide opportunities for hiring professional monitors and crafting formal rules.

Created2016-02-01
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We investigate fundamental nonlinear dynamics of ferrofluidic Taylor-Couette flow - flow confined be-tween two concentric independently rotating cylinders - consider small aspect ratio by solving the ferro-hydrodynamical equations, carrying out systematic bifurcation analysis. Without magnetic field, we find steady flow patterns, previously observed with a simple fluid, such as those

We investigate fundamental nonlinear dynamics of ferrofluidic Taylor-Couette flow - flow confined be-tween two concentric independently rotating cylinders - consider small aspect ratio by solving the ferro-hydrodynamical equations, carrying out systematic bifurcation analysis. Without magnetic field, we find steady flow patterns, previously observed with a simple fluid, such as those containing normal one- or two vortex cells, as well as anomalous one-cell and twin-cell flow states. However, when a symmetry-breaking transverse magnetic field is present, all flow states exhibit stimulated, finite two-fold mode. Various bifurcations between steady and unsteady states can occur, corresponding to the transitions between the two-cell and one-cell states. While unsteady, axially oscillating flow states can arise, we also detect the emergence of new unsteady flow states. In particular, we uncover two new states: one contains only the azimuthally oscillating solution in the configuration of the twin-cell flow state, and an-other a rotating flow state. Topologically, these flow states are a limit cycle and a quasiperiodic solution on a two-torus, respectively. Emergence of new flow states in addition to observed ones with classical fluid, indicates that richer but potentially more controllable dynamics in ferrofluidic flows, as such flow states depend on the external magnetic field.

ContributorsAltmeyer, Sebastian (Author) / Do, Younghae (Author) / Lai, Ying-Cheng (Author)
Created2017-01-06
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We investigate the dynamics of ferrofluidic wavy vortex flows in the counter-rotating Taylor-Couette system, with a focus on wavy flows with a mixture of the dominant azimuthal modes. Without external magnetic field flows are stable and pro-grade with respect to the rotation of the inner cylinder. More complex behaviors can

We investigate the dynamics of ferrofluidic wavy vortex flows in the counter-rotating Taylor-Couette system, with a focus on wavy flows with a mixture of the dominant azimuthal modes. Without external magnetic field flows are stable and pro-grade with respect to the rotation of the inner cylinder. More complex behaviors can arise when an axial or a transverse magnetic field is applied. Depending on the direction and strength of the field, multi-stable wavy states and bifurcations can occur. We uncover the phenomenon of flow pattern reversal as the strength of the magnetic field is increased through a critical value. In between the regimes of pro-grade and retrograde flow rotations, standing waves with zero angular velocities can emerge. A striking finding is that, under a transverse magnetic field, a second reversal in the flow pattern direction can occur, where the flow pattern evolves into pro-grade rotation again from a retrograde state. Flow reversal is relevant to intriguing phenomena in nature such as geomagnetic reversal. Our results suggest that, in ferrofluids, flow pattern reversal can be induced by varying a magnetic field in a controlled manner, which can be realized in laboratory experiments with potential applications in the development of modern fluid devices.

ContributorsAltmeyer, Sebastian (Author) / Do, Younghae (Author) / Lai, Ying-Cheng (Author) / Ira A. Fulton Schools of Engineering (Contributor)
Created2015-12-21