DOP008 Dietary manipulation of the healthy human and colitic murine gut microbiome by CD-TREAT diet and exclusive enteral nutrition; a proof of concept study

Objectives. The objectives of this proof of concept study were to (a) examine the temporal changes in fatigue and diversity of the gut microbiome over the course of chemoradiotherapy (CRT) in adults with rectal cancers; (b) investigate whether there are differences in diversity of the gut microbiome between fatigued and nonfatigued participants at the middle and at the end of CRT; and (c) investigate whether there are differences in the relative abundance of fecal microbiota at the phylum and genus levels between fatigued and nonfatigued participants at the middle and at the end of CRT. Methods. Stool samples and symptom ratings were collected prior to the inception of CRT, at the middle (after 12–16 treatments) and at the end (after 24–28 treatments) of the CRT. Descriptive statistics and Mann–Whitney U test were computed for fatigue. Gut microbiome data were analyzed using the QIIME2 software. Results. Participants (N = 29) ranged in age from 37 to 80 years. The median fatigue score significantly changed at the end of CRT (median = 23.0) compared with the median score before the initiation of CRT for the total sample (median = 17.0; p≤0.05). At the middle of CRT, the alpha diversity (abundance of Operational Taxonomic Units) was lower for fatigued participants (149.30 ± 53.1) than for nonfatigued participants (189.15 ± 44.18, t(23) = 2.08, p≤0.05). A similar trend was observed for the Shannon and Faith diversity indexes at the middle of CRT. However, at the end of CRT, there were no significant differences for any alpha diversity indexes between fatigued and nonfatigued participants. Proteobacteria, Firmicutes, and Bacteroidetes were the dominant phyla for fatigued participants, and Escherichia, Bacteroides, Faecalibacterium, and Oscillospira were the most abundant genera for fatigued participants. Conclusion. CRT-associated perturbation of the gut microbiome composition may contribute to fatigue.

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O-05: Metagenomic analysis of the gut microbiome during a course of Exclusive Enteral Nutrition (EEN) provides novel insights on mechanism of EEN action

Journal of Crohn s and Colitis ◽

10.1016/s1873-9946(14)50003-7 ◽

2014 ◽

Vol 8 ◽

pp. S393-S394

Author(s):

K. Gerasimidis ◽

N. Loman ◽

J. Quick ◽

S.T. Calus ◽

U. Ijaz ◽

...

Keyword(s):

Enteral Nutrition ◽

Gut Microbiome ◽

Metagenomic Analysis ◽

Exclusive Enteral Nutrition

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AN INULIN-TYPE FRUCTAN ENRICHED EXCLUSIVE ENTERAL NUTRITION FORMULA SUPPRESSES COLITIS THROUGH GUT MICROBIOME MODULATION AND PROMOTING EXPANSION OF ANTI-INFLAMMATORY T CELL SUBSETS

10.1101/2021.02.02.429403 ◽

2021 ◽

Author(s):

Genelle R. Healey ◽

Kevin Tsai ◽

Daniel J. Lisko ◽

Laura Cook ◽

Bruce A. Vallance ◽

...

Keyword(s):

T Cells ◽

T Cell ◽

Enteral Nutrition ◽

Gut Microbiome ◽

T Cell Subsets ◽

Transfer Model ◽

Mucus Layer ◽

Exclusive Enteral Nutrition ◽

Therapeutic Benefits ◽

Anti Inflammatory

AbstractBackground & AimsExclusive enteral nutrition (EEN) is used to treat pediatric Crohn’s disease (CD), but therapeutic benefits are not long lasting. Due to reported lower efficacy EEN is not routinely used to treat pediatric ulcerative colitis (UC). Inulin-type fructans (IN) beneficially modulate the gut microbiome and promote expansion of anti-inflammatory immune cells. We hypothesized that enriching EEN with IN (EENIN) would enhance treatment efficacy. To test this, we examined the effects of EEN-IN on colitis development, the gut microbiome and CD4+ T cells using an adoptive T cell transfer model of colitis.MethodsTCR-ß deficient mice were randomized to one of four groups: 1) Control, 2) Chow, 3) EEN and 4) EEN-IN, and naïve CD4+ T cells were adoptively transferred into groups 2-4, after which mice were monitored for 5-weeks prior to experimental endpoint.ResultsMice fed EEN-IN showed greater colitis protection, with colonic shortening, goblet cell and crypt density loss reduced over that of EEN fed mice and reduced disease activity and immune cell infiltration compared to chow fed mice, and less crypt hyperplasia and higher survival compared to both groups. EENIN mice maintained colonic mucus layer thickness and had increased levels of Foxp3+IL-10+ and Rorγt+IL- 22+ and reduced levels of Tbet+IFNγ+ and Tbet+TNF+ CD4+ T cells. EEN-IN also lead to higher butyrate, Bifidobacterium spp. and Bacteroides spp. concentrations.ConclusionThe EEN-IN group showed reduced colitis development as compared to the chow and EEN groups. This highlights the potential benefits of EEN-IN as a novel induction therapy for pediatric CD and UC patients.SynopsisWe demonstrated that inulin-type fructan enriched exclusive enteral nutrition formula reduced colitis development likely due to butyrate-dependent pathways that helped preserve the mucus layer and promote an anti-inflammatory intestinal environment via expansion of regulatory T cells.

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Parasites modulate the gut-microbiome in insects: A proof-of-concept study

PLoS ONE ◽

10.1371/journal.pone.0227561 ◽

2020 ◽

Vol 15 (1) ◽

pp. e0227561 ◽

Cited By ~ 6

Author(s):

Brian L. Fredensborg ◽

Inga Fossdal í Kálvalíð ◽

Thor B. Johannesen ◽

C. Rune Stensvold ◽

Henrik V. Nielsen ◽

...

Keyword(s):

Gut Microbiome ◽

Proof Of Concept ◽

Concept Study

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Bacterial Taxa and Functions Are Predictive of Sustained Remission Following Exclusive Enteral Nutrition in Pediatric Crohn’s Disease

Inflammatory Bowel Diseases ◽

10.1093/ibd/izaa001 ◽

2020 ◽

Vol 26 (7) ◽

pp. 1026-1037 ◽

Cited By ~ 6

Author(s):

Casey M A Jones ◽

Jessica Connors ◽

Katherine A Dunn ◽

Joseph P Bielawski ◽

André M Comeau ◽

...

Keyword(s):

Machine Learning ◽

Crohn’S Disease ◽

Species Richness ◽

Crohn's Disease ◽

Enteral Nutrition ◽

Treatment Response ◽

Clinical Data ◽

Gut Microbiome ◽

Sustained Remission ◽

Exclusive Enteral Nutrition

Abstract Background The gut microbiome is extensively involved in induction of remission in pediatric Crohn’s disease (CD) patients by exclusive enteral nutrition (EEN). In this follow-up study of pediatric CD patients undergoing treatment with EEN, we employ machine learning models trained on baseline gut microbiome data to distinguish patients who achieved and sustained remission (SR) from those who did not achieve remission nor relapse (non-SR) by 24 weeks. Methods A total of 139 fecal samples were obtained from 22 patients (8–15 years of age) for up to 96 weeks. Gut microbiome taxonomy was assessed by 16S rRNA gene sequencing, and functional capacity was assessed by metagenomic sequencing. We used standard metrics of diversity and taxonomy to quantify differences between SR and non-SR patients and to associate gut microbial shifts with fecal calprotectin (FCP), and disease severity as defined by weighted Pediatric Crohn’s Disease Activity Index. We used microbial data sets in addition to clinical metadata in random forests (RFs) models to classify treatment response and predict FCP levels. Results Microbial diversity did not change after EEN, but species richness was lower in low-FCP samples (<250 µg/g). An RF model using microbial abundances, species richness, and Paris disease classification was the best at classifying treatment response (area under the curve [AUC] = 0.9). KEGG Pathways also significantly classified treatment response with the addition of the same clinical data (AUC = 0.8). Top features of the RF model are consistent with previously identified IBD taxa, such as Ruminococcaceae and Ruminococcus gnavus. Conclusions Our machine learning approach is able to distinguish SR and non-SR samples using baseline microbiome and clinical data.

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