Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| Name | Class |
|---|---|
| University of Minnesota | OTHER |
Not provided
Not provided
Not provided
Not provided
The purpose of this study is to determine if adding dietary fiber, such as inulin, to a diet that does not have enough fiber would raise the levels of potentially beneficial bacteria, such as Bifidobacterium, in the gut. There is evidence to suggest that these microbes can affect gut health and immune response, including to vaccines. The investigators will examine how inulin in the diet (compared to the maltodextrin control) (1) causes changes in the composition and function of the gut microbes, (2) reduces gut inflammation and gut leakiness caused by the vaccine, (3) increases immune response to vaccination, and (4) changes the expression of important adhesion molecules on the surface of white blood cells. Intestinal and whole-body responses will be measured in all participants.
Inulin, a dietary fiber supplement, is known to increase gut levels of potentially beneficial bacteria, including Bifidobacterium that are indigenous to gut microbiomes. Our underlying hypothesis is that the commensal microbiome, including Bifidobacterium, in the proximal colon or distal ileum affects the environment of draining lymph nodes and can thus modulate immune responses, including to vaccines. In the current study, participants will consume 12 grams/day inulin or maltodextrin (control) for 3 weeks before the administration of the Ty21a typhoid fever vaccine, 1 week during the vaccine, and 1 week after the vaccine. Vaccine response will be measured by counting T cells and immunoglobulin G (IgG) or immunoglobulin A (IgA)-secreting plasma cells specific for Ty21a. Gut permeability will be measured at baseline, and before and after the vaccine administration. Systemic inflammation and immune activation will be measured by analyzing blood for markers of inflammation.
Not provided
Not provided
Not provided
Not provided
| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Inulin and Ty21a Vaccine | Experimental | Participants will consume 12 grams/day of inulin for 3 weeks before the administration of the Ty21a vaccine, 1 week during the vaccine, and 1 week after the vaccine for a total of 5 weeks. |
|
| Maltodextrin and Ty21a Vaccine | Placebo Comparator | Participants will consume 12 grams/day of maltodextrin (control) for 3 weeks before the administration of the Ty21a vaccine, 1 week during the vaccine, and 1 week after the vaccine for a total of 5 weeks. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Inulin | Dietary Supplement | Consume 12 grams/day of inulin for 5 weeks (Day 9 - 43). |
|
| Measure | Description | Time Frame |
|---|---|---|
| Change in vaccine-specific antibody-secreting cell response to oral Ty21a typhoid vaccination using the standard 4-dose regimen | Measurement of baseline level (Day 26; before first vaccine dose) and post-vaccine, antibody response, Immunoglobulin G (IgG), Immunoglobulin M (IgM) and IgA, 7 and 9 days after the first vaccine dose using the antibody-in-lymphocyte-supernatant (ALS) assay to identify antibody-secreting cells in blood. Two antigens will be used: Ty21a outer membrane protein and lipopolysaccharide from Salmonella Typhi. | Day 26, 37, and 39 |
| Measure | Description | Time Frame |
|---|---|---|
| Change in vaccine-specific serum antibody response to typhoid vaccination | Measurement of baseline level (Day 26; before first vaccine dose) and post-vaccine (28 d after first vaccine dose) antibody levels (IgG, IgM, IgA) | Day 26 and 58 |
| Change in vaccine-specific fecal IgA antibody levels from typhoid vaccination |
Not provided
Inclusion Criteria:
Body Mass Index (BMI) 18.5 - 30.9 kg/m2
inadequate total dietary fiber intake defined as:
Exclusion Criteria:
Not provided
Not provided
Not provided
Not provided
Not provided
| Name | Affiliation | Role |
|---|---|---|
| Danielle Lemay, PhD | USDA, ARS, Western Human Nutrition Research Center | Principal Investigator |
| Ryan Snodgrass, PhD | USDA, ARS, Western Human Nutrition Research Center | Principal Investigator |
| Mary Kable, PhD | USDA, ARS, Western Human Nutrition Research Center | Principal Investigator |
| Bess Caswell, PhD | USDA, ARS, Western Human Nutrition Research Center | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| USDA, ARS, Western Human Nutrition Research Center | Davis | California | 95616 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 19690573 | Background | Meyer D, Stasse-Wolthuis M. The bifidogenic effect of inulin and oligofructose and its consequences for gut health. Eur J Clin Nutr. 2009 Nov;63(11):1277-89. doi: 10.1038/ejcn.2009.64. Epub 2009 Aug 19. | |
| 20591206 | Background | Costabile A, Kolida S, Klinder A, Gietl E, Bauerlein M, Frohberg C, Landschutze V, Gibson GR. A double-blind, placebo-controlled, cross-over study to establish the bifidogenic effect of a very-long-chain inulin extracted from globe artichoke (Cynara scolymus) in healthy human subjects. Br J Nutr. 2010 Oct;104(7):1007-17. doi: 10.1017/S0007114510001571. Epub 2010 Jul 1. |
Not provided
Not provided
Not provided
| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| ICF | No | No | Yes | Informed Consent Form | Mar 10, 2025 | Dec 2, 2025 | ICF_000.pdf |
Not provided
| ID | Term |
|---|---|
| D007249 | Inflammation |
| D014435 | Typhoid Fever |
| ID | Term |
|---|---|
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |
| D012480 | Salmonella Infections |
| D004756 | Enterobacteriaceae Infections |
Not provided
Not provided
| ID | Term |
|---|---|
| D007444 | Inulin |
| C008315 | maltodextrin |
| C072772 | Ty21a typhoid vaccine |
| ID | Term |
|---|---|
| D013213 | Starch |
| D005936 | Glucans |
| D001704 | Biopolymers |
| D011108 | Polymers |
| D046911 |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| Maltodextrin | Dietary Supplement | Consume 12 grams/day of maltodextrin for 5 weeks (Day 9 - 43). |
|
|
| Ty21a Typhoid Fever Vaccine | Biological | All participants will receive the vaccine. One capsule is swallowed on alternate days, e.g. days 30, 32, 34, and 36 for a total of 4 capsules. |
|
|
Measurement of baseline level (Day 26; before first vaccination dose) and change in fecal antibody levels |
| Day 26, 39, and 58 |
| Change in plasma cytokines as markers of systemic inflammation | Measurement of plasma cytokines, such as interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-alpha), and IL-1beta | Day 8, 26, 37, 39, and 58 |
| Change in plasma acute phase proteins and adhesion molecules | Measurement of acute phase reactants, such as C-reactive protein (CRP) and serum amyloid-A (SAA), and intercellular adhesion molecules, such as intercellular adhesion molecule-1 (ICAM-1) and vascular endothelial cell adhesion molecule-1 (VCAM-1) | Day 8, 26, 37, 39, and 58 |
| Change in a plasma marker of lipopolysaccharide (LPS) exposure | Measurement of plasma LPS-binding protein using an ELISA. | Day 8, 26, 37, 39, and 58 |
| Change in blood monocyte subsets | Monocyte subsets will be analyzed using flow cytometry. | Day 8, 26, 37, 39, and 58 |
| Change in plasma short chain fatty acids (SCFA) | Plasma SCFA will be measured using liquid chromatography-mass spectrometry (LC-MS). | Day 8, 26, 37, 39, and 58 |
| Change in urinary lactulose and D-mannitol | Measurement of lactulose to mannitol ratio, an indicator of intestinal permeability, in urine | Day 8, 26, and 37 |
| Change in fecal microbiome | Measurement of relative abundance of colonic bacteria using DNA isolated from stool. | Period 1: Days 1-7; Period 2: Days 16-25; Period 3: Days 26-36; Period 4: Days 37-43; Period 5: Days 58-65 |
| Change in fecal mRNA | Total RNA, and specifically, messenger ribonucleic acid (mRNA), will be analyzed from preserved stools. | Period 1: Days 1-7; Period 2: Days 16-25; Period 3: Days 26-36; Period 4: Days 37-43; Period 5: Days 58-65 |
| Change in stool consistency and frequency | Measurement of stool consistency using the Bristol stool scale, a medical tool used to classify stool forms into 7 categories, and frequency via self-report in diaries. | Period 1: Days 1-7; Period 2: Days 16-25; Period 3: Days 26-36; Period 4: Days 37-43; Period 5: Days 58-65 |
| Change in GI symptoms | Measurement of GI symptoms using a 10-symptom health questionnaire with degree of discomfort ranked in one of four categories (0 absent, 1 mild, 2 moderate, or 3 severe; PMID: 9301412) | Period 1: Days 1-7; Period 2: Days 16-25; Period 3: Days 26-36; Period 4: Days 37-43; Period 5: Days 58-65 |
| Change in fecal pH | Measurement of fecal pH using a standard pH meter. | Period 1: Days 1-7; Period 2: Days 16-25; Period 3: Days 26-36; Period 4: Days 37-43; Period 5: Days 58-65 |
| Change in fecal calprotectin | Measurement of calprotectin will be done by ELISA | Period 1: Days 1-7; Period 2: Days 16-25; Period 3: Days 26-36; Period 4: Days 37-43; Period 5: Days 58-65 |
| Change in fecal SCFA | Measurement of SCFA will be done by gas chromatography-mass spectrometry (GC-MS.) | Period 1: Days 1-7; Period 2: Days 16-25; Period 3: Days 26-36; Period 4: Days 37-43; Period 5: Days 58-65 |
| Change in fecal metabolites | Measurement of bile acids and other metabolites will be measured | Period 1: Days 1-7; Period 2: Days 16-25; Period 3: Days 26-36; Period 4: Days 37-43; Period 5: Days 58-65 |
| Change in fecal secretory total immunoglobulin A (sIgA) | Measurement of total fecal sIgA using ELISA. | Period 1: Days 1-7; Period 2: Days 16-25; Period 3: Days 26-36; Period 4: Days 37-43; Period 5: Days 58-65 |
| 23135760 | Background | Dewulf EM, Cani PD, Claus SP, Fuentes S, Puylaert PG, Neyrinck AM, Bindels LB, de Vos WM, Gibson GR, Thissen JP, Delzenne NM. Insight into the prebiotic concept: lessons from an exploratory, double blind intervention study with inulin-type fructans in obese women. Gut. 2013 Aug;62(8):1112-21. doi: 10.1136/gutjnl-2012-303304. Epub 2012 Nov 7. |
| 26203099 | Background | Holscher HD, Bauer LL, Gourineni V, Pelkman CL, Fahey GC Jr, Swanson KS. Agave Inulin Supplementation Affects the Fecal Microbiota of Healthy Adults Participating in a Randomized, Double-Blind, Placebo-Controlled, Crossover Trial. J Nutr. 2015 Sep;145(9):2025-32. doi: 10.3945/jn.115.217331. Epub 2015 Jul 22. |
| 17268410 | Background | Kolida S, Meyer D, Gibson GR. A double-blind placebo-controlled study to establish the bifidogenic dose of inulin in healthy humans. Eur J Clin Nutr. 2007 Oct;61(10):1189-95. doi: 10.1038/sj.ejcn.1602636. Epub 2007 Jan 31. |
| 10801918 | Background | Menne E, Guggenbuhl N, Roberfroid M. Fn-type chicory inulin hydrolysate has a prebiotic effect in humans. J Nutr. 2000 May;130(5):1197-9. doi: 10.1093/jn/130.5.1197. |
| 27492975 | Background | Micka A, Siepelmeyer A, Holz A, Theis S, Schon C. Effect of consumption of chicory inulin on bowel function in healthy subjects with constipation: a randomized, double-blind, placebo-controlled trial. Int J Food Sci Nutr. 2017 Feb;68(1):82-89. doi: 10.1080/09637486.2016.1212819. Epub 2016 Aug 5. |
| 22743314 | Background | Petry N, Egli I, Chassard C, Lacroix C, Hurrell R. Inulin modifies the bifidobacteria population, fecal lactate concentration, and fecal pH but does not influence iron absorption in women with low iron status. Am J Clin Nutr. 2012 Aug;96(2):325-31. doi: 10.3945/ajcn.112.035717. Epub 2012 Jun 27. |
| 25002669 | Background | Huda MN, Lewis Z, Kalanetra KM, Rashid M, Ahmad SM, Raqib R, Qadri F, Underwood MA, Mills DA, Stephensen CB. Stool microbiota and vaccine responses of infants. Pediatrics. 2014 Aug;134(2):e362-72. doi: 10.1542/peds.2013-3937. Epub 2014 Jul 7. |
| 30674610 | Background | Huda MN, Ahmad SM, Alam MJ, Khanam A, Kalanetra KM, Taft DH, Raqib R, Underwood MA, Mills DA, Stephensen CB. Bifidobacterium Abundance in Early Infancy and Vaccine Response at 2 Years of Age. Pediatrics. 2019 Feb;143(2):e20181489. doi: 10.1542/peds.2018-1489. |
| 28856924 | Background | Zuckerman JN, Hatz C, Kantele A. Review of current typhoid fever vaccines, cross-protection against paratyphoid fever, and the European guidelines. Expert Rev Vaccines. 2017 Oct;16(10):1029-1043. doi: 10.1080/14760584.2017.1374861. |
| 23408152 | Background | Fiorentino M, Lammers KM, Levine MM, Sztein MB, Fasano A. In vitro Intestinal Mucosal Epithelial Responses to Wild-Type Salmonella Typhi and Attenuated Typhoid Vaccines. Front Immunol. 2013 Feb 12;4:17. doi: 10.3389/fimmu.2013.00017. eCollection 2013. |
| 30443257 | Background | Salerno-Goncalves R, Galen JE, Levine MM, Fasano A, Sztein MB. Manipulation of Salmonella Typhi Gene Expression Impacts Innate Cell Responses in the Human Intestinal Mucosa. Front Immunol. 2018 Nov 1;9:2543. doi: 10.3389/fimmu.2018.02543. eCollection 2018. |
| D016905 | Gram-Negative Bacterial Infections |
| D001424 | Bacterial Infections |
| D001423 | Bacterial Infections and Mycoses |
| D007239 | Infections |
| Macromolecular Substances |
| D004040 | Dietary Carbohydrates |
| D002241 | Carbohydrates |
| D005630 | Fructans |
| D011134 | Polysaccharides |