Deanna L. Gibson’s research while affiliated with University of British Columbia - Okanagan and other places

The intricate balance between the gut microbiome and host health inspires innovations in drug development. Commensal bacteria provide a multi-targeted approach ideal for treating complex medical conditions, like inflammatory bowel disease (IBD). These bacteria are self-replicating factories with broad targets that promote balanced intestinal inflammation, mucosal barrier function, and eubiosis. Yet, the lack of superiority to gold-standard treatments and their clinical inconsistency makes most probiotics unreliable for disease treatments. Intestinal inflammation, a driving factor in many diseases, often overwhelms commensal bacteria, which lack the stress-resistance mechanisms necessary to withstand host immune defenses. To address this, we introduced a persistence platform BioPersist™ into E. coli Nissle 1917. We hypothesized that a bio-engineered probiotic, or genetically engineered microbial medicine (GEMM™), designed to persist during inflammation would enhance probiotic bioavailability during colitis, leading to sustained therapeutic outcomes. We evaluated BioPersist in multiple translational colitis models such as in mice and pigs. BioPersist delayed the onset and reduced the severity of both chronic and acute colitis, proving more effective than 5-aminosalicylate. BioPersist thrived during inflammation promoting tolerogenic immune responses that limited infiltrating leukocyte activity and decreased TNF-α from resident myeloid cells in the mesentery. The persistence feature of BioPersist allowed the probiotic to overcome the damaging inflammatory response, eliciting mucosal healing evident by the increase in microbially-derived butyric acid. Based on these preclinical results, BioPersist may be a novel therapeutic option for both human and veterinary applications that sustains efficacy during colitis. One Sentence Summary Adding a persistence feature to a probiotic enhances its efficacy for colitis treatment, enhancing future human and veterinary therapeutic applications.

Glyphosate, a widely used herbicide in North America, has become prevalent in the food supply due to preharvest applications, raising concerns about potential health impacts. This study investigated the effects of prenatal glyphosate exposure on the gut bacteriome, colitis, metabolic health, and behavior across generations in mice. In healthy mice, glyphosate decreased goblet cell numbers and mucin-2 expression in the colon and dysregulated cytokines in F1 and F2 progeny at levels below the EPA acceptable daily limit. Glyphosate also disrupted metabolism, including impaired glucose tolerance, increased insulin resistance and reduced serum GLP-1 levels. Moreover, prenatal glyphosate exposure induced behavioral deficits, including reduced locomotor activity and impaired working memory, which are associated with alterations in the gut microbiome composition and key gut-brain axis mediators. These data underscore the potential risks associated with glyphosate exposure, highlighting the need for further research and regulatory consideration.

Background: Indian immigration to westernized countries has surged in recent years, with this demographic facing a higher risk of Inflammatory Bowel Disease (IBD) after migration. Studying the gut microbiome is crucial to understanding the factors contributing to IBD, yet Indians remain underrepresented in microbiome research, Objective: This study investigates the gut microbiome of Indians residing in India, Indian immigrants in Canada, and Canadians of Indian ancestry to understand the impact of westernization on their gut. Given the higher risk of IBD among Indo-Canadians, these results provide insight into how westernization of the gut microbiome may influence incidence of IBD. Stool samples were collected from healthy Indians in India, Indian Immigrants in Canada, Indo-Canadians, plus Canadian-borne individuals with European descent and Euro-Immigrants as non-Indian/westernized controls (N = 174). 16S rRNA gene and shotgun sequencing compared microbial taxa and functional profiles across groups. Dietary and demographic data were collected to assess lifestyle patterns. Results: Indians and Indo-Immigrants had distinct gut microbiotas from westernized groups, with high abundances of Prevotella spp. and a CAZyme profile reflecting their traditional high complex carbohydrate diet. The Indian microbiome also showed characteristics of high bacterial cell turnover, pathogenic potential, and stress tolerance, indicating their gut may be better primed to handle stressors on the gut. Indo-Canadians displayed a transitional microbiome towards westernization, which followed a pattern of increasing dietary acculturation. Conclusions: The shift from a non-westernized to westernized microbiome in Indo-Canadians highlights the significant influence that westernization and dietary acculturation has on the gut microbiome. Given that 44% of the Canadian population is made up of first- and second-generation immigrants and westernized practices are being adopted worldwide, future research should investigate the health implications that such microbiome transitions have on immigrant populations and newly industrialized nations.

Objective This study investigates the gut microbiome of Indians residing in India, Indian immigrants in Canada, and Canadians of Indian ancestry to understand the impact of westernization on their gut. Given the higher risk of Inflammatory Bowel Disease (IBD) among Indo-Canadians, these results provide insight into how westernization of the gut microbiome may influence incidence of IBD. Design Stool samples were collected from healthy Indians in India, Immigrants born in India, Indo-Canadians, plus Canadian-borne individuals with European descent and Euro-Immigrants as non-Indian/westernized controls (N = 174).16S and shotgun sequencing compared microbial taxa and functional profiles across groups. Dietary and demographic data were collected to assess lifestyle patterns. Results The microbiome of Indians and Indo-Immigrants were found to be distinct from westernized groups, with high abundances of Prevotella spp. and CAZymes known to facilitate the breakdown of plant-based foods, reflecting their traditional high complex carbohydrate diet. The Indian microbiome also showed characteristics of high bacterial cell turnover, pathogenic potential and stress tolerance, indicating their gut may be better primed to handle stressors on the gut. Indo-Canadians exhibited a transitional gut microbiome, harbouring taxa both common to Indians and westernized groups, which followed a pattern of increasing dietary acculturation. Conclusions The transition from a non-westernized to westernized microbiome in Canadian- borne Indian migrants highlights the significant influence that the westernized lifestyle and dietary acculturation has on the gut microbiome. Considering globalization and immigration to westernized countries is occurring at a rapid rate, with 40.6% of the Canadian population made up of first- and second-generation immigrants, ¹ future research should investigate the health implications that such microbiome transitions have on immigrant populations and newly industrialized nations. KEY MESSAGES What is already known on this topic The Indian microbiota, known for its high Prevotella spp. abundances, differs from the westernized gut. Indians in westernized countries face increased risk for Inflammatory Bowel Disease (IBD), which may be linked to their gut microbiome. Yet, research on this demographic is scarce, leaving a gap in knowledge to elucidate the factors contributing to their increased IBD risk. What this study adds Our study, using both 16S and shotgun metagenomic analysis, reveal a decline in Prevotella spp. and a loss of gut robustness in Indian migrants, indicating a transition towards a westernized microbiome. This transition is characterized by the diminished capacity for carbohydrate-active enzymes (CAZymes) necessary for plant-based dietary products, which was associated with their transition away from the high-fiber Indian diet. How this might affect research, practice, or policy By highlighting the microbiome changes that occur in Indian immigrants upon westernization, this study underscores the urgent need for more inclusive microbiome research beyond westernized/European populations, which can inform healthcare strategies to mitigate disease risks associated with westernization.

The O-glycoprotein Mucin-2 (MUC2) forms the protective colon mucus layer. While animal models have demonstrated the importance of Muc2, few studies have explored human MUC2 in similar depth. Recent studies have revealed that secreted MUC2 is bound to human feces. We hypothesized human fecal MUC2 (HF-MUC2) was accessible for purification and downstream structural and functional characterization. We tested this via histologic and quantitative imaging on human fecal sections; extraction from feces for proteomic and O-glycomic characterization; and functional studies via growth and metabolic assays in vitro. Quantitative imaging of solid fecal sections showed a continuous mucus layer of varying thickness along human fecal sections with barrier functions intact. Lectin profiling showed HF-MUC2 bound several lectins but was weak to absent for Ulex europaeus 1 (α1,2 fucose-binding) and Sambucus nigra agglutinin (α2,6 sialic acid-binding), and did not have obvious b1/b2 barrier layers. HF-MUC2 separated by electrophoresis showed high molecular weight glycoprotein bands (∼1–2 MDa). Proteomics and Western analysis confirmed the enrichment of MUC2 and potential MUC2-associated proteins in HF-MUC2 extracts. MUC2 O-glycomics revealed diverse fucosylation, moderate sialylation, and little sulfation versus porcine colonic MUC2 and murine fecal Muc2. O-glycans were functional and supported the growth of Bacteroides thetaiotaomicron (B. theta) and short-chain fatty acid (SCFA) production in vitro. MUC2 could be similarly analyzed from inflammatory bowel disease stools, which displayed an altered glycomic profile and differential growth and SCFA production by B. theta versus healthy samples. These studies describe a new non-invasive platform for human MUC2 characterization in health and disease.

Fasting diets (FDs) have drawn great attention concerning their contribution to health and disease over the last decade. Despite considerable interest in FDs, the effect of fasting diets on eating behaviors, sleep, and mood-essential components of diet satisfaction and mental health- has not been addressed comprehensively. Understanding the critical role that fasting plays in these elements will open up potential treatment avenues that have not yet been explored. The aim of the present paper was to conduct a comprehensive critical review exploring the effects of fasting on eating behaviors, sleep, and mood. There is currently a lack of clarity regarding which fasting option yields the most advantageous effects, and there is also a scarcity of consistent trials that assess the effects of FDs in a comparable manner. Similarly, the effects and/or treatment options for utilizing FDs to modify eating and sleep behaviors and enhance mood are still poorly understood. Further researches aiming at understanding the impacts of various fasting regimes, providing new insights into the gut-brain axis and offering new treatment avenues for those with resistant anxiety and depression, are warranted. Alteration of eating behaviors can have lasting effects on various physiological parameters. The use of fasting cures can underpin ancient knowledge with scientific evidence to form a new approach to the prevention and treatment of problems associated with co-morbidities or challenges pertaining to eating behaviors. Therefore, a thorough examination of the various fasting regimens and how they impact disease patterns is also warranted.

Background & aims: Dietary patterns are important in managing ulcerative colitis (UC), given their influence on gut microbiome-host symbiosis and inflammation. We investigated whether the Mediterranean Diet Pattern (MDP) vs the Canadian Habitual Diet Pattern (CHD) would impact disease activity, inflammation and the gut microbiome in patients with quiescent UC. Methods: We performed a prospective, randomized control trial in adults (65% female; median age 47 y) with quiescent UC in an outpatient setting from 2017 to 2021. Participants were randomized to a MDP (n=15) or CHD (n=13) for 12 weeks. Disease activity (Simple Clinical Colitis Activity Index) and fecal calprotectin (FC) were measured at baseline and week 12. Stool samples were analyzed by 16S rRNA gene amplicon sequencing. Results: The diet was well-tolerated by the MDP group. At week 12, 75% (9/12) of participants in the CHD had a FC >100 μg/g, versus 20% (3/15) of participants in the MDP group. The MDP group had higher levels of total fecal short-chain fatty acids (SCFAs) (p=0.01), acetic acid (p=0.03) and butyric acid (p=0.03) compared to the CHD. Furthermore, the MDP-induced alterations in microbial species associated with a protective role in colitis (Alistipes finegoldii and Flavonifractor plautii), as well as the production of SCFAs (Ruminococcus bromii). Conclusions: A MDP induces gut microbiome alterations associated with the maintenance of clinical remission and reduced FCin patients with quiescent UC. The data supports that a MDP is a sustainable diet pattern that could be recommended as a maintenance diet and adjunctive therapy for UC patients in clinical remission. ClinicalTrials.gov no: NCT0305371.

In January 2022, a group of experts came together to discuss current perspectives and future directions in nutritional immunology as part of a symposium organized by the Canadian Nutrition Society. Objectives included (1) creating an understanding of the complex interplay between diet and the immune system from infants through to older adults, (2) illustrating the role of micronutrients that are vital to the immune system, (3) learning about current research comparing the impact of various dietary patterns and novel approaches to reduce inflammation, autoimmune conditions, allergies, and infections, and (4) discussing select dietary recommendations aimed at improving disease-specific immune function. The aims of this review are to summarize the symposium and to identify key areas of research that require additional exploration to better understand the dynamic relationship between nutrition and immune function.

Background The Mediterranean diet pattern (MDP) is believed to improve health and promote balanced inflammation and metabolism. While unknown, compelling evidence suggests that MDP could benefit patients with inflammatory bowel disease (IBD). We aimed to evaluate the level of diet adherence, diet quality, and nutritional adequacy of the MDP in patients with Ulcerative Colitis (UC). Methods Adult participants (n = 32) with quiescent UC were randomized to follow a MDP (n = 18) or Canadian Habitual Diet (CHD) (n = 14) for 12 weeks. The MDP participants received tailored nutrition education from a Registered Dietitian. Demographic, clinical data, medical history, and quality of life were assessed with the Short Inflammatory Bowel Disease Questionnaire (SIBDQ), dietary adherence with the Mediterranean Diet Serving Score (MDSS), diet quality via the Healthy Eating Index-2015 (HEI-2015), and dietary intake (ASA-24) were completed at baseline and week 12. Results Participants’ diets were analyzed (MDP n = 15, CHD n = 13). The MDP (n = 10, 67%) achieved a high level of adherence (MDSS score between 16 and 24) vs. CHD (n = 3), (p = 0.030). HEI-2015 significantly increased from baseline to week 12 (p = 0.007) in the MDP and was significantly higher at week 12 compared to the CHD (p = 0.0001). The SIBDQ (bowel domain) showed reductions in the passage of large amounts of gas (p = 0.01) and improvements in tenesmus (p = 0.03) in the MDP. Despite enhanced diet quality and adherence in the MDP, females had inadequate intakes of calcium, iron, vitamin D, vitamin E, and choline and males had inadequate intakes of fiber, vitamin D, vitamin E, and choline. No adverse events were reported. Conclusion With nutrition education, high adherence to the MDP was achieved without an increase in bowel symptoms. Following the MDP led to a higher diet quality; however, nutritional inadequacies were identified. Tailored dietary education focusing on nutrients of concern when following the MDP is recommended to ensure nutritional adequacy. Clinical trial registration [www.ClinicalTrials.gov], identifier [NCT03053713].