The Relationships among Diet, Bacterial Taxa, Fecal Short Chain Fatty Acids (SCFA) and Symptoms among Healthy Women and Women with Irritable Bowel Syndrome
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Abstract
Irritable bowel syndrome (IBS) is the most prevalent gastrointestinal (GI) disorder in western developed countries exerting a tremendous economic, social, and emotional burden. IBS, a disorder of gut-brain interaction (DGBI), characterized by abdominal pain and altered bowel habits, is one of the top 10 reasons for primary care consultations. IBS affects nearly 35 million Americans (10% to 15% adults), incurring $20 billion in direct and indirect expenditures. Sex is a major risk factor for IBS; women experience more visceral pain and hypersensitivities than men. Two-thirds of the IBS population in the US are women, the majority in their reproductive years, and tend to report psychological comorbidities (anxiety and depression). Most of the IBS population seek multiple, conventional treatments to manage their IBS symptoms. There is increasing evidence for the effectiveness of a high fiber diet in reducing IBS symptoms, especially constipation. How a high dietary fiber (DF) intake affects IBS symptoms at a molecular level is not clear. Several studies have shown strong, empirical evidence that diet modifies the gut microbiome, however additional clinical research is warranted to confirm these laboratory findings. This study employed secondary analysis for the purpose of exploring the relationships between fecal short chain fatty acids (SCFA) and IBS clinical symptoms (i.e., constipation, diarrhea, abdominal pain), stool microbiome (based on 16S ribosomal DNA data), and DF intake, as well as in comparison group of healthy controls (HC). The results add to the evidence base for higher fiber intake as an effective therapeutic intervention for the management of IBS symptoms, strengthen current evidence of the presence of gut dysbiosis in IBS, and could further advance nursing science and symptom management. The long-term goal of this line of research was to fill the gaps as described above. The specific aims of this research study included: Aim1) To compare fecal SCFA concentrations (millimolar) between IBS and HC groups. Aim 2) Separately within each IBS bowel pattern subgroup (IBS-C, IBS-D) and HC, determine the associations between (2a) SCFAs and GI symptoms, (2b) SCFAs (millimole) and DF (soluble and insoluble in grams) intake, (2c) DF (soluble and insoluble in grams) and GI symptoms (diarrhea, constipation, pain) and Aim 3) To explore the relationships of fecal SCFA metabolites with fecal bacteria taxa at the genus level in IBS bowel pattern subgroups (IBS-D and IBS-C) and HC groups. Hypotheses tested included: 1) IBS cohorts regardless of bowel group will have reduced fecal SCFA compared to HC (Aim 1); 2) lower total SCFA will be associated with higher abdominal pain severity (Aim 2a); 3) higher total SCFA will be associated with diarrhea, while lower total SCFA will be associated with constipation (Aim 2a). It was also expected that a DF intake above 25g/day will have higher SCFA fecal concentration as compared to <25g/day (Aim 2b). Also, a high and rapidly fermentable and soluble DF intake will be positively correlated with fecal SCFA concentrations and IBS abdominal pain severity (Aim 2c). Higher intake of insoluble and slowly fermentable DF intake will be associated with lower abdominal pain (Aim 2c). Aim 3 is exploratory. Given the nature of this study, causality cannot be established; however, this study provides some degree of evidence that gut dysbiosis exists in women with IBS in this sample. Current knowledge claims that humans and the gut microbes are co-dependent with each other and alteration in gut microbiome has been associated with several inflammatory disorders including IBS. Confirmation of microbiome signature in IBS; however, is still ongoing and this observational study helps affirm some of these biological signatures. Specifically, this study found positive associations of high fecal butyrate concentration and reduced GI symptoms and non-GI symptoms in women with IBS. This finding is important because IBS is a gut-brain interaction disorder and currently, there is limited research in investigating the links of psychological distress symptom markers and the gut microbiome in IBS. This study supports the idea that gut commensals are indispensable to health and since diet modulates the gut microbiome, the development of evidence-based personalized dietary interventions is key in managing IBS symptoms. The generated fecal metabolomics data provided valuable information about mechanisms in which the microbiome influences clinical symptoms of IBS.
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Thesis (Ph.D.)--University of Washington, 2024
