Clostridioides Difficile Infection Levi Teigen PhD RD May 11 2021 Objectives Recognize the nutritional implications of a C difficile infection at both a systemic and local ie colonic level ID: 1043916
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1. Nutritional Management of Patients Following Microbiota Transplant Therapy to Treat Clostridioides Difficile InfectionLevi Teigen, PhD, RDMay 11, 2021
2. ObjectivesRecognize the nutritional implications of a C. difficile infection at both a systemic and local (i.e. colonic) levelBe introduced to microbiota transplant therapy (MTT)Be able to identify nutritional targets following MTT therapy for C. difficile infection
3. Clostridioides Difficile is the most common cause of antibiotic-associated diarrheaGerding and Lessa 2015 Infect Dis Clin N AmGerding and Lessa 2015 Infect Dis Clin N AmGuh et al. 2020 NEJM
4. CDI exploits inflammation and microbial dysbiosisFerreyra et al. 2014 Cellular MicrobiologyFischer 2017 Gastroenterology and HepatologyStecher and Hardt 2011 Curr Opin MicrobiolFerreyra et al. 2014 Cell Microbiol
5. Very little work has been done on the nutritional consequences of CDISevere diarrheaAbdominal painWeight lossDiminished functional statusBartlett 2002 NEJMSoes et al. 2014 Eur J Clin Microb Infect DisBauer et al. 2009 Clin Microbiol Infect
6. Limited data suggests malnutrition is prevalent, increases risk, and contributes to worse outcomes in CDIPrevalence >50%1,2 Increased risk of CDI development3-7 and recurrent CDI8Independent risk factor for mortality9-111Hickey and Corish 2011 Proceedings of the Nutrition Society; 2Wong et al. 2009 Proceedings of the Nutrition Society; 3Lee et al. 2020 Eur J Gastro Hepatol; 4Buchner and Sonnenberg 2001 Am J Gastro; 5Li et al. 2016 JAMA Surg; 6Schneider et al. 2004 British Journal of Nutrition; 7Van Esch et al. 2015 Archives of Public Health; 8Behar et al. 2017 J Inf; 9Bielakova et al. 2016 Wien Klin Wochenschr; 10Perez-Cruz et al. 2018 Clin Nutr; 11Appaneal et al. 2018 OFID
7. Nutritional management of CDI requires a new clinical nutrition paradigm
8. CDI illustrates potential consequences of a singular focus on nutrition status of the hostTeigen et al. 2018 J Parenter Enteral Nutr“Provision of adequate protein is crucial for optimizing outcomes in hospitalized patients”Kuchnia et al. 2018 J Parenter Enteral NutrTeigen et al. 2018 J Parenter Enteral Nutr
9.
10. CDI requires correction of “luminal malnutrition”Protein: Intestinal barrier function Metabolic demands of inflammationMicrobiota-accessible CHOs:Necessary to support recovery of gut microbiome
11. Microbiota accessible CHO is critical to CDI outcomes regardless of proteinMoore et al. 2015 PLoS ONE
12. Fiber intervention reduces C difficile burden at 30% calories from protein levelHryckowian et al. 2018 Nat Microbiol
13. A high-protein, low CHO diet exacerbates CDI40% protein; 6% CHO30% protein; 57% CHOMefferd et al. 2020 mSystems
14. Current therapeutic approach perpetuates microbiota injury and can result in recurrent CDI
15. FMT progressed from crude preparation to simple encapsulated, shelf-stable microbiota2010201220152018University of Minnesota Microbiota Therapeutics Program
16. The UMN Microbiota Therapeutics Program uses cGMP protocols for our productsDonor programProduction SuiteQA and Material Release
17. Standardized work-flow ensures that every unit is made the same way and every lot has a batch record and retained samples
18. Clinical ApplicationsrCDIUlcerative ColitisLeukemiaLiver DiseaseAutism Spectrum DisorderPitt Hopkins SyndromeLung CancerSolid Organ Transplant RecipientsParkinson’s Disease
19. MTT for CDI reintroduces competition for nutrients addressing “Metabolic Niche”Weingarden et al. 2014 Am J Physiol Gastrointest Liver Physiol
20. MTT for CDI reintroduces mechanisms of direct inhibitionSCFAsSecondary BAsSeektaz et al. 2018 Anaerobe
21. Nutrition Management Post-MTT: Post-Infectious IBS is a common problemGas/bloating and irregular BMs commonRole for FODMAP?Food avoidance commonWadhwa et al. 2016 Aliment Pharmacol Ther; Halmos et al. 2015 Gut; Staudacher et al. 2012 J Nutr
22. Post-MTT diet intended to support new microbes and accommodate GI symptomsEmphasize soft, fiber-containing foodsChew wellSmall, frequent snacks/mealsAvoid foods high in fat/sugarAvoid artificial sweetenersAvoid alcoholMinimize highly processed foods Lewis and Heaton 1999 Dig Dis and SciEarle et al. 2015 Cell Host and MicrobeEarle et al. 2015 Cell Host and Microbe; Lewis and Heaton 1999 Dig Dis and Sci
23. Role for calories and protein in supporting recovery following MTT has not been exploredAlang and Kelly et al. 2015 OFID; Fischer et al. 2018 Clinical Gastroenterology and Hepatology
24. ConclusionsC. difficile infection results in physiological changes that predispose patients to malnutrition/muscle wastingC. difficile infection requires a new model of clinical nutrition that supports the host through the indigenous microbiotaMicrobiota transplant therapy is an effective therapy for recurrent C. difficile infection and is being studied in a growing number of clinical conditionsPost-infectious IBS is common following MTT, but nutrient flow to transplanted microbes is important to maintain
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