Köln, University, Diss., 2004.

Inflammatory bowel disease (IBD), characterised by chronic intestinal inflammation, is hypothesised to arise from the interplay between susceptibility genes, the immune system, environmental factors, and gut microbiota. Akkermansia muciniphila is a symbiotic bacterium that accounts for 1-5% of the human fecal microbiota. This microbe has been hailed as a next-generation probiotic, principally with regards to its plethora of beneficial host interactions, including the ability to influence mucin secretion and strengthen the intestinal barrier. Though a clear-cut role and mechanism by which A. muciniphila influences inflammatory conditions is unknown, evidence indicates this microbe is depleted in IBD, suggesting it may have protective effects that are lost in these conditions. Here, we investigate the role and mechanism of A. muciniphila in intestinal inflammation and its influence on intestinal barrier function by utilizing barrier-disrupting models of colitis, including dextran sulphate sodium (DSS) and Trichuris muris. Though only minor benefits were derived from this microbe in germ-free mice, in specific pathogen-free (SPF) mice, administration of pasteurized A. muciniphila in a DSS recovery model ameliorated inflammation severity and promoted recovery compared to controls. When gavaged prior to DSS administration, both live and pasteurized A. muciniphila failed to diminish inflammatory markers indicating minimal preventative effects. T. muris-infected SPF mice treated with live A. muciniphila showed increased levels of Th2 and anti-inflammatory cytokines, decreased worm burden, and enhanced levels of the mucin, Muc5ac, compared with those receiving control broth or pasteurized bacteria. Further, both live and pasteurized A. muciniphila ameliorated the severity of inflammation in mucin 2 deficient (Muc2-/-) mouse model of spontaneous colitis, indicating that these protective effects are Muc2-independent. These observations provide us not only with an enhanced understanding of the role A. muciniphila plays in the pathogenesis of intestinal inflammatory conditions but also may fuel novel avenues of treatment for those with IBD. / Thesis / Master of Science (MSc) / Akkermansia muciniphila is a bacterium that accounts for 1-5% of the human fecal microbiota and has been shown to stimulate intestinal mucus production and strengthen the gut barrier. Though several studies have linked inflammatory bowel disease (IBD) with decreased levels of A. muciniphila, the precise role of this microbe in gut inflammation is unknown. In this research, we investigate the role of A. muciniphila in gut barrier function and inflammation. Across several experimental models, we find that supplementation with live, and in some cases, pasteurized A. muciniphila, can help curb established inflammation and promote a more anti-inflammatory gut environment. We also identify that these changes are independent of this bacteria’s ability to influence mucin 2, the main building block of intestinal mucus. This study has the potential to both enhance our understanding of microbial influence in intestinal inflammation and may also lead to the development of future treatments for IBD.

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Autism spectrum disorder (ASD) is characterized by deficits in social communication and interaction as well as by repetitive patterns of behavior. It is thought to affect 1 in 68 children in the United States, yet researchers do not know what causes it and treatments are primarily focused on alleviating symptoms associated with ASD rather than treating any underlying cause. Various theories have been proposed over the years regarding what causes ASD in the hopes of finding effective treatment options. One of these theories, and the topic of this work, is that the intestinal bacteria play a role in the development of autism. The idea that gut bacteria may play a role in health and disease is one that has been gaining increased interest lately, and this has spread to the field of autism research. Reports of children with ASD suffering from gastrointestinal (GI) issues are widespread, and even the first reports of children with ASD mentioned that some of them experienced GI symptoms or had issues with feeding. While GI symptoms are uncomfortable for any child, they pose special circumstances for those with ASD because these children are likely unable to effectively communicate what they are experiencing. This thesis will first review the prevalence of GI issues in children with ASD as well as discuss studies that have examined if there is a difference between the gut bacteria of children with ASD compared to neurotypical children. As will be shown, many studies have in fact found a significant difference, but these differences vary across studies and a consensus has not been reached. Following this, the link between the gut bacteria and the brain, as well as how this relates to ASD will be discussed. Then, an overview of various treatment studies aimed at targeting the gut bacteria in animal models of ASD as well as in children with ASD will be analyzed. While this field of research is certainly exciting, there is still a lot of work to be done by researchers. For one, the wide range of methodologies used and populations studied introduces variables that could be skewing the results and contributing to the lack of agreement between researchers regarding what bacterial strains might be relevant to ASD. Additionally, just because there is a correlation between certain bacterial strains and ASD does not mean it can be assumed that this is causing the development of ASD in so many children. Nonetheless, the fact that some treatment studies have led to improvements in ASD-related behaviors when targeting the gut bacteria of children indicates that this field of research is worthy of attention and continued support.

F-theory is a twelve-dimensional geometric version of string theory and is believed to be a natural framework for GUT model building. The aim of this dissertation is to study how gauge theories realized by F-theory can accommodate GUT models. In this dissertation, we focus on local and semi-local GUT model building in F-theory. For local GUT models, we build SU(5) GUTs by using abelian U(1) fluxes via the SU(6) gauge group. Doing so, we obtain non-minimal spectra of the MSSM with doublet-triplet splitting by switching on abelian U(1)2 fluxes. We also classify all supersymmetric U(1)2 fluxes by requiring an exotic-free bulk spectrum. For semi-local GUT models, we start with an E8 singularity and obtain lower rank gauge groups by unfolding the singularity governed by spectral covers. In this framework, the spectra can be calculated by the intersection numbers of spectral covers and matter curves. In particular, we use SU(4) spectral covers and abelian U(1)X fluxes to build flipped SU(5) models. We show that three-generation spectra of flipped SU(5) models can be achieved by turning on suitable fluxes. To construct E6 GUTs, we consider SU(3) spectral covers breaking E8 down to E6. Also three-generation extended MSSM can be obtained by using non-abelian SU(2) × U(1)2 fluxes.

In captivity the diversity of prey items for obligate insectivores is limited and nutritionally inadequate, leading to nutrient deficiencies. Zoological institutions utilize gut-loading, an insect supplementation technique, to compensate for these nutrient shortcomings. This study developed a gut-loading diet (GLD) to enhance the nutritive quality of the domestic house cricket (Acheta domestica) for insectivorous amphibians and reptiles, with the requisite that it also met cricket foraging and palatability needs. Gut-loaded cricket analysis established its effectiveness such that the targeted level of most nutrients required by the end consumers were met after consuming the diet for 24 hrs (Ca:P of 1.127; vitamin A (retinyl acetate) level of 12,607 IU/kg; vitamin E level of 342 IU/kg and a linoleic fatty acid level of 4.62%), peaking at 2 days for some and remained above targeted amounts for at least 4 days. A list of cricket gut-loading optimization husbandry procedures has also been recommended.