Alzheimer’s Disease is a devastating disease and a major medical challenge of the 21st century without preventative treatment available and absence of a cure. Due to the profound clinical impact on patients with the disease, and emotional and financial impact on their loved ones, there has been extensive research into therapeutic agents. Unfortunately, many of the studies are abandoned or fail due to a lack of complete understanding of the complex pathophysiology of Alzheimer’s Disease, and ineffective drug targets. While the etiology of disease remains controversial, the accumulation of both amyloid beta protein and neurofibrillary tangles has been the most supported theory for the past thirty years. Also in recent years, the gut microbiome has gained much attention for its unexplored potential and role in health and disease, and the Mediterranean Diet has been deemed the “healthiest” diet for the sixth consecutive year by health experts. This study reviews the current understood pathophysiology of AD and standard diagnostic criteria. This thesis aims to provide an overview of the neuroprotective effects of the Mediterranean Diet, the alterations of the gut microbiome that are associated with the Mediterranean Diet, and the alterations of the gut microbiome associated with Alzheimer’s Disease. Based on the analysis of the large number of studies presented, this thesis concludes that the Mediterranean Diet optimally modifies the ratio of Firmicutes:Bacteroidetes in the gut of people with Alzheimer’s Disease and reduces pathological and symptomatic progression of disease.

This project evaluated the feasibility of salvaging zebra mussel-infested freshwater mussels from their native habitat by determining 1) how zebra mussel infestation affects unionid feeding and body condition, 2) how starvation in quarantine affects body condition of unionids, and 3) what feeding regime maintain unionid condition in quarantine. The effects of zebra mussel infestation on two mussel species were evaluated through glycogen analyses of mantle tissue and gut content analysis. Specimens of Amblema p. plicata (Say, 1817) and Quadrula p. pustulosa (I. Lea, 1831), collected from a heavily infested reach of the Ohio River in 1996, had significantly lower (p<0.05) glycogen levels than specimens collected from a low-infestation reach upstream. In 1996 and 1997, heavily infested Amblema p. plicata and Quadrula p. pustulosa had significantly less (p<0.01) organic matter and fewer algal cells in their guts than lightly infested specimens. In addition, gut contents of individual A. p. plicata contained significantly less (p<0.05) organic matter and fewer algal cells than the combined gut contents of all zebra mussels (18-33 mm in length) attached to their shells. Gut analyses also revealed significant diet overlap between native unionids and infesting zebra mussels. Thus, competitive interactions or interference by zebra mussels likely reduced unionid ingestion and consequently reduced glycogen stores. During quarantine, unionids salvaged from a lightly infested area and starved for 30 days had glycogen levels that declined dramatically. After 30 days without supplemental feeding, mean glycogen levels of A. p. plicata declined 85%, and mean glycogen levels of Q. p. pustulosa declined 70%. Thus, feeding of unionids is necessary to maintain their condition during lengthy quarantine. To determine the best feeding regime for unionids in quarantine, assimilation efficiencies and carbon budgets were established for the rainbow mussel, Villosa iris (Lea, 1829), using radio-labelled cultures of Neochloris oleoabundans (Chantanachat and Bold 1962) at three cell concentrations. Assimilation efficiencies for Villosa iris at 100,000cells/ml, 10,000 cells/ml, and 1,000 cells/ml were similar (45-56%); however, regardless of these similarities, assimilation efficiencies from this study indicate that Neochloris oleoabundans is readily assimilated (~50% AE) by Villosa iris . In addition, total assimilation was maximized at 100,000cells/ml, which indicates that Villosa iris has the greatest amount of energy available for growth, reproduction, and maintenance of condition in captivity at this cell concentration. During a second quarantine experiment, specimens were provided with 100,000cells/ml of N. oleoabundans twice per day. Initial mean glycogen levels for Amblema p. plicata (9.4 + 2.4 mg/g) and Quadrula p. pustulosa collected from ORM 175.5 in July 1997 were not significantly different (p>0.3) than the mean glycogen levels of A. p. plicata and Q. p. pustulosa collected from the same site in July 1996. Glycogen stores of unionids entering quarantine, therefore, were similar in both the starvation and controlled feeding experiments. After 7, 14, and 30 days of controlled feeding in quarantine, mean glycogen levels of A. p. plicata and Q. p. pustulosa did not change significantly (p>0.1). Thus, quarantine protocol for salvaged native mussels should include the feeding of algae to captive specimens to sustain glycogen levels prior to relocation. / Master of Science

Honeybees (Apis mellifera L.) are the major insect pollinators of many different crops. A drastic decline in the honey bee populations has been reported over the past decade. While many factors have contributed to this decline, pesticides, poor nutrition, and Varroa mites are the most common concerns noted by scientists and beekeepers. Aside from direct toxicity from pesticides, it has been observed that sublethal pesticide doses have effects on honey bee physiology and behavior such as oxidative stress, disruption of foraging and homing, and changes to honey bee neurophysiology. The primary objectives of this project were to examine honey bee gut microbiome, physiology, and pesticide exposure along an agricultural intensification gradient and to examine the interactive impacts of pesticide exposure and poor nutrition on honey bees in a controlled laboratory cage setting. Sixteen honey bee colonies were placed in four locations across Mississippi with varying degrees of natural forage availability.

A healthy gut microbiome is crucial for the development, growth, and health of dairy calves; however, diarrhea in pre-weaned calves is highly prevalent, difficult to treat, and causes detrimental effects to the dairy industry. This study characterized early gut microbiota using longread-based 16S rRNA gene sequencing and investigated its associations with calf diarrhea and colostrum microbiota. The full-length 16S rRNA gene was amplified and sequenced on a Nanopore sequencer. We identified shared bacterial species in colostrum and calf feces, whose abundance in calf feces reduced with age. Diarrheic calves exhibited differing gut diversity before, during, and after diarrhea, and harbored increased bacteria resistant to the Cefotaxime antibiotic. Several bacterial species were associated with age and calf health. Additionally, a machine learning model identified bacteria to predict diarrhea. This study will be useful for the goal of reducing antibiotic use to promote gut health and prevent and treat neonatal calf diarrhea.

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Antimicrobial resistance poses a significant challenge to human health and is also a pressing One Health concern. The routine use of antibiotics as growth promoters in agricultural animals has contributed to the emergence of antibiotic resistance, which can subsequently affect human populations. Discontinuing this practice has led to a surge in infections and therapeutic antibiotic use in these animals. This increased susceptibility to infections may be linked, at least partially, to the loss of colonization resistance resulting from alterations in the microbiome. This study focuses on poultry, as the consumption of chicken meat can introduce antibiotic-resistant microbes into the human population. The overarching hypothesis for this research project is that a rationally designed consortium of microbes sourced from healthy chickens will increase colonization resistance and decrease susceptibility to infections as an alternative to growth-promoting antibiotics. The first goal was to analyze the broiler chicken’s gut microbiome and to establish a comprehensive culture collection of microorganisms from healthy chickens. Culture-enriched and culture-independent 16S sequencing was applied to assess the cultivability of the samples and to analyze their microbial profiles. Isolates were identified using MALDI-TOF and 16S rRNA gene sequencing. Frozen samples (from antibiotic-free farms) had a greater microbial diversity than fresh samples (from a university research facility). However, a greater proportion of the microbiome was recovered by culture from the fresh compared to the frozen samples. A strain collection of 1121 isolates representing 121 species was constructed. In Aim 2, I carried out a functional screen to identify isolates from the culture collection that inhibited the growth of the predominant poultry pathogens, E. coli and C. perfringens. Several isolates were identified that inhibited one or the other pathogens and a small number of isolates killed both pathogens. These microbes form the basis of therapeutic consortia to increase colonization resistance in chickens. / Thesis / Master of Science (MSc) / In the poultry industry, antibiotics have been used to promote chicken’s growth. This has contributed to the spread of antibiotic resistance to animal/human pathogens. When the use of growth-promoting antibiotics is stopped, the chickens become more susceptible to infections. These chickens have possibly lost protective bacteria that help fight pathogens. I thought that bacteria from healthy chicken’s intestine could help fight pathogens. To do this, I isolated a large collection of chicken gut’s good bacteria from healthy birds after individually separating them from the mixture using growing methods and sequencing. I separated bacteria from frozen and fresh mixtures, found that more bacteria grow from fresh mixtures. I then tested individual bacteria from this collection to see if they stop pathogenic bacteria like E. coli and C. perfringens from growing. I found that many bacteria could do this which may be used to develop a therapeutic community of good bugs to colonize chickens to make them more disease resistant.

Research on adolescent drinking shows that younger people are at greater risk of developing behavioral deficiencies that can be detrimental to their social relationships and health over time. Recent research has shown that changes within the microbiome-gut-brain axis (MGB) can affect social behavior. These changes involve microbiota populations that influence addictive behaviors after prolonged substance intake through neurochemical shifts that extend through the nervous, circulatory, and immune system. Using Massey's biosocial model, I aim to expand on the relationship between the MGB axis, social behavior, and adolescent alcohol use disorder through a meta-theoretical approach. I explore the strengths and shortcomings of Massey's biosocial model of segregation and stratification and its use of the allostatic load model, telomere length, and gene exposure to develop a stronger theoretical concept using the micro-gut-brain axis as a conceptual foundation. Can the MGB-axis model be used to identify potential pathways in which alcohol use disorder (AUD) persists from adolescence to adulthood? I find that adolescent drinking leads to changes in microbiota populations that are known to influence AUDs and increases the development of diseases such as liver disease and its effects on social behavior. The MGB axis can help us understand the effects of substance and dietary habits on disease and illness by connecting life science knowledge and sociological perspectives. With this modern application of cognitive sociology, I have shown that future research on addictive behaviors should consider the application of biomarker data to further expand on new theoretical and methodological approaches in the study of disease and addiction.

京都大学 / 新制・課程博士 / 博士(農学) / 甲第24906号 / 農博第2569号 / 新制||農||1102(附属図書館) / 学位論文||R5||N5469 / 京都大学大学院農学研究科森林科学専攻 / (主査)教授 大村 和香子, 教授 髙野 俊幸, 教授 飛松 裕基 / 学位規則第4条第1項該当 / Doctor of Agricultural Science / Kyoto University / DGAM

Tidigare forskning har visat ett samband mellan vår tarmflora och vår fysiska hälsa, och idag görs även mycket forskning på om den även kan påverka vår mentala hälsa. Idag lider över fyra procent av världens befolkning av depression, och den här litteraturstudien har, genom att analysera sju studier och deras resultat, försökt få svar på frågan om probiotika kan lindra depression. Antingen som primär behandling eller som komplement till annan behandling. Den här litteraturstudien gav inga konkreta svar på den frågan, annat än att alla inblandade forskare är överens om att det behövs göra fler, längre och större studier innan man kan dra några slutsatser. / Previous research has shown a connection between our microbiota and physical health, and today a lot of research is also being done on whether it also can affect our mental health. Today, over four percent of the world's population suffers from depression, and this literature study has, by analysing seven studies and their results, attempted to answer the question of whether probiotics can alleviate depression. Either as primary treatment or as a supplement to other treatment. This literature study did not provide any definite answers to that question, other than that all the researchers involved in the studies analysed agree that more, longer and larger studies are needed before one can draw any conclusions.

Alzheimer’s disease (AD) is the most common form of dementia and a growing disease burden that has seen pharmacological interventions primarily fail. Instead, it has been suggested that preventative measures such as a healthy diet may be the best way in preventing AD. Prebiotics are one such potential measure and are fermented into metabolites by the gut microbiota and acting as gut-brain axis components, beneficially impact the brain. However, the impact of prebiotics in AD prevention is unknown. Here we show that the prebiotic inulin increased multiple gut-brain axis components such as scyllo-inositol and short chain fatty acids in the gut, periphery, and in the case of scyllo-inositol, the brain. We found in E3FAD and E4FAD mice fed either a prebiotic or control diet for 4-months, that the consumption of the prebiotic inulin can beneficially alter the gut microbiota, modulate metabolic function, and dramatically increase scyllo-inositol in the brain. This suggests that the consumption of prebiotics can beneficially impact the brain by enhancing metabolism, helping to decrease AD risk factors.