scholarly journals The Role of Gut Microbiome Perturbation in Fatigue Induced by Repeated Stress from Chemoradiotherapy: A Proof of Concept Study

2020 ◽  
Vol 2020 ◽  
pp. 1-13
Author(s):  
Velda J. González-Mercado ◽  
Josué Pérez-Santiago ◽  
Debra Lyon ◽  
Israel Dilán-Pantojas ◽  
Wendy Henderson ◽  
...  

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.

mBio ◽  
2021 ◽  
Vol 12 (3) ◽  
Author(s):  
Lauren E. Fuess ◽  
Stijn den Haan ◽  
Fei Ling ◽  
Jesse N. Weber ◽  
Natalie C. Steinel ◽  
...  

ABSTRACT Commensal microbial communities have immense effects on their vertebrate hosts, contributing to a number of physiological functions, as well as host fitness. In particular, host immunity is strongly linked to microbiota composition through poorly understood bi-directional links. Gene expression may be a potential mediator of these links between microbial communities and host function. However, few studies have investigated connections between microbiota composition and expression of host immune genes in complex systems. Here, we leverage a large study of laboratory-raised fish from the species Gasterosteus aculeatus (three-spined stickleback) to document correlations between gene expression and microbiome composition. First, we examined correlations between microbiome alpha diversity and gene expression. Our results demonstrate robust positive associations between microbial alpha diversity and expression of host immune genes. Next, we examined correlations between host gene expression and abundance of microbial taxa. We identified 15 microbial families that were highly correlated with host gene expression. These families were all tightly correlated with host expression of immune genes and processes, falling into one of three categories—those positively correlated, negatively correlated, and neutrally related to immune processes. Furthermore, we highlight several important immune processes that are commonly associated with the abundance of these taxa, including both macrophage and B cell functions. Further functional characterization of microbial taxa will help disentangle the mechanisms of the correlations described here. In sum, our study supports prevailing hypotheses of intimate links between host immunity and gut microbiome composition. IMPORTANCE Here, we document associations between host gene expression and gut microbiome composition in a nonmammalian vertebrate species. We highlight associations between expression of immune genes and both microbiome diversity and abundance of specific microbial taxa. These findings support other findings from model systems which have suggested that gut microbiome composition and host immunity are intimately linked. Furthermore, we demonstrate that these correlations are truly systemic; the gene expression detailed here was collected from an important fish immune organ (the head kidney) that is anatomically distant from the gut. This emphasizes the systemic impact of connections between gut microbiota and host immune function. Our work is a significant advancement in the understanding of immune-microbiome links in nonmodel, natural systems.


2020 ◽  
Vol 4 (Supplement_2) ◽  
pp. 1595-1595
Author(s):  
Sabrina Trudo ◽  
Rosa Moreno ◽  
Jeong Hoon Pan ◽  
Daniel Gallaher ◽  
Jae Kyeom Kim ◽  
...  

Abstract Objectives Cruciferous (CRU; rich in glucosinolates) and apiaceous (API; rich in furanocoumarins) vegetable intake decrease colon cancer risk markers, likely through different mechanisms. Previous reports suggest background diets influence efficacy of bioactives. Here, we determined the effects on the composition of the gut microbiome of CRU and API supplementation to different background diets, diet-induced obesity (DIO) and the total western diet (TWD). Methods C57BL/6J male mice were fed standard diet (AIN93G), DIO, DIO with 21% (w/w) CRU (DIO + CRU), DIO with 21% (w/w) API (DIO + API), TWD, TWD with CRU (TWD + CRU), or TWD with API (TWD + API). After 12 weeks, cecal contents were collected for 16S rRNA sequencing and data analyzed by mothur. Results There were no differences in body weight gain except mice fed DIO + CRU gained more than mice fed AIN-93G or TWD. Lachnospiraceae was increased by CRU supplementation to both DIO and TWD and by API supplementation to TWD. CRU increased alpha diversity [Shannon Index, number of observed Operational Taxonomic Unit (OTUs)] compared to DIO and TWD. Regarding beta diversity, DIO + CRU showed distinct cluster compared to DIO (Bray-Curtis, ANOSIM, R = 0.35, P < 0.001; Jaccard distance, R = 0.47, P < 0.001). TWD + CRU showed distinct cluster compared to TWD (Bray-Curtis, R = 0.59, P < 0.001; Jaccard distance, R = 0.62, P < 0.001). API did not change alpha diversity, but did affect beta diversities with distinct clusters between API groups and their basal diet groups (Jaccard distance, R = 0.36 and 0.31 for DIO and TWD, respectively, P < 0.05). Among top 25 discriminating features between DIO and TWD and their supplementation of API and CRU, there were 9 shared OTUs including Lachnospiraceae, Clostridium XlVa, Clostridiales, Eisenbergiella, and Clostridium IV. Akkermansia were decreased in DIO + CRU compared with DIO. In TWD panel, Bifidobacterium and Erysipelotrichaceae decreased in TWD + CRU, while Turicibacter were identified as TWD + CRU signature. Erysipelotrichaceae and Bifidobacterium differentiated AIN-93G, DIO, and TWD. Conclusions CRU supplementation of DIO and TWD altered gut microbiome composition with some differences based on background diet. API also altered composition, albeit to a lesser extent. Funding Sources University of Arkansas, Fulbright Nicaragua Fellow.


2020 ◽  
Vol 23 (1) ◽  
pp. 31-41
Author(s):  
Velda J. González-Mercado ◽  
Wendy A. Henderson ◽  
Anujit Sarkar ◽  
Jean Lim ◽  
Leorey N. Saligan ◽  
...  

Purpose: To examine a) whether there are significant differences in the severity of symptoms of fatigue, sleep disturbance, or depression between patients with rectal cancer who develop co-occurring symptoms and those with no symptoms before and at the end of chemotherapy and radiation therapy (CRT); b) differences in gut microbial diversity between those with co-occurring symptoms and those with no symptoms; and c) whether before-treatment diversity measurements and taxa abundances can predict co-occurrence of symptoms. Methods: Stool samples and symptom ratings were collected from 31 patients with rectal cancer prior to and at the end of (24–28 treatments) CRT. Descriptive statistics were computed and the Mann-Whitney U test was performed for symptoms. Gut microbiome data were analyzed using R’s vegan package software. Results: Participants with co-occurring symptoms reported greater severity of fatigue at the end of CRT than those with no symptoms. Bacteroides and Blautia2 abundances differed between participants with co-occurring symptoms and those with no symptoms. Our random forest classification (unsupervised learning algorithm) predicted participants who developed co-occurring symptoms with 74% accuracy, using specific phylum, family, and genera abundances as predictors. Conclusion: Our preliminary results point to an association between the gut microbiota and co-occurring symptoms in rectal cancer patients and serves as a first step in potential identification of a microbiota-based classifier.


2020 ◽  
Vol 41 (5) ◽  
pp. 678-685 ◽  
Author(s):  
Pei-pei Zhang ◽  
Lin-lin Li ◽  
Xue Han ◽  
Qin-wei Li ◽  
Xu-hua Zhang ◽  
...  

2021 ◽  
Vol 5 (Supplement_2) ◽  
pp. 1151-1151
Author(s):  
Marina Brown ◽  
Ginger Reeser ◽  
Leila Shinn ◽  
Matthew Browning ◽  
Andiara Schwingel ◽  
...  

Abstract Objectives Urbanization has reduced environmental microorganism exposure, with most Americans spending over 90% of their time indoors. However, gardening remains a viable means of exposure to soil microorganisms and harvesting of edible produce. Accordingly, we aimed to determine relations between gardening, dietary habits, and gut microbiota. Methods Gardening families (N = 10) and non-gardening (control) families (N = 9) were enrolled in a longitudinal pilot trial. Families included two adults and a child (5–18 years) for a total sample size of 54 participants. Fecal samples were collected prior to and at the end of the gardening season. Garden soil samples (n = 9) were collected prior to and at the end of the season. Diet history questionnaires were collected at the beginning and end of the study to measure Healthy Eating Index (HEI) scores. Fecal and soil DNA were extracted, sequenced (V4 region of 16S rDNA gene), and analyzed using DADA2 and QIIME2. Alpha diversity measures were assessed, including Faith's phylogenetic diversity (PD) and observed operational taxonomic units (OTUs). Results Gardening families had significantly more fecal OTUs compared to control families (172.3 ± 44.2 vs. 157.0 ± 44.2, respectively; P = 0.03). Gardening families had greater (P = 0.02) Faith's PD scores and tended (P = 0.08) to have more fecal OTUs than the control group at peak gardening season. In the gardening families, fecal OTUs and Faith's PD were numerically but not statistically greater at the end of the season compared to baseline (all p’s > 0.05). Prior to the gardening season, gardening adults had greater HEI scores compared to control families (57 ± 9.1 vs. 49 ± 8.8, P = 0.03). HEI scores were not different between groups at the end of the study. Conclusions This study revealed that the fecal microbiota of families that garden differs from non-gardening families, and there are detectable changes in the fecal microbial community of gardeners and their family members over the course of the gardening season. Further research is needed to understand the role of diet in these changes and if microbes within the soil move between the soil and gastrointestinal environments. Funding Sources This research was funded by the Christopher Family Foundation Food and Family Grant Program.


2021 ◽  
Vol 8 ◽  
Author(s):  
Jason W. Arnold ◽  
Hunter D. Whittington ◽  
Suzanne F. Dagher ◽  
Jeffery Roach ◽  
M. Andrea Azcarate-Peril ◽  
...  

Complex dietary carbohydrate structures including β(1–4) galacto-oligosaccharides (GOS) are resistant to digestion in the upper gastrointestinal (GI) tract and arrive intact to the colon where they benefit the host by selectively stimulating microbial growth. Studies have reported the beneficial impact of GOS (alone or in combination with other prebiotics) by serving as metabolic substrates for modulating the assembly of the infant gut microbiome while reducing GI infections. N-Acetyl-D-lactosamine (LacNAc, Galβ1,4GlcNAc) is found in breast milk as a free disaccharide. This compound is also found as a component of human milk oligosaccharides (HMOs), which have repeating and variably branched lactose and/or LacNAc units, often attached to sialic acid and fucose monosaccharides. Human glycosyl-hydrolases do not degrade most HMOs, indicating that these structures have evolved as natural prebiotics to drive the proper assembly of the infant healthy gut microbiota. Here, we sought to develop a novel enzymatic method for generating LacNAc-enriched GOS, which we refer to as humanized GOS (hGOS). We showed that the membrane-bound β-hexosyl transferase (rBHT) from Hamamotoa (Sporobolomyces) singularis was able to generate GOS and hGOS from lactose and N-Acetyl-glucosamine (GlcNAc). The enzyme catalyzed the regio-selective, repeated addition of galactose from lactose to GlcNAc forming the β-galactosyl linkage at the 4-position of the GlcNAc and at the 1-position of D-galactose generating, in addition to GOS, LacNAc, and Galactosyl-LacNAc trisaccharides which were produced by two sequential transgalactosylations. Humanized GOS is chemically distinct from HMOs, and its effects in vivo have yet to be determined. Thus, we evaluated its safety and demonstrated the prebiotic's ability to modulate the gut microbiome in 6-week-old C57BL/6J mice. Longitudinal analysis of gut microbiome composition of stool samples collected from mice fed a diet containing hGOS for 5 weeks showed a transient reduction in alpha diversity. Differences in microbiome community composition mostly within the Firmicutes phylum were observed between hGOS and GOS, compared to control-fed animals. In sum, our study demonstrated the biological synthesis of hGOS, and signaled its safety and ability to modulate the gut microbiome in vivo, promoting the growth of beneficial microorganisms, including Bifidobacterium and Akkermansia.


2021 ◽  
Author(s):  
Koen F. Dekkers ◽  
Sergi Sayols-Baixeras ◽  
Gabriel Baldanzi ◽  
Christoph Nowak ◽  
Ulf Hammar ◽  
...  

The human gut microbiota produces a variety of small compounds, some of which enter the bloodstream and impact host health. Conversely, various exogenous nutritional and pharmaceutical compounds affect the gut microbiome composition before entering circulation. Characterization of the gut microbiota—host plasma metabolite interactions is an important step towards understanding the effects of the gut microbiota on human health. However, studies involving large and deeply phenotyped cohorts that would reveal such meaningful interactions are scarce. Here, we used deep metagenomic sequencing and ultra-high-performance liquid chromatography linked to mass spectrometry for detailed characterization of the fecal microbiota and plasma metabolome, respectively, of 8,584 participants invited at age 50 to 64 of the Swedish CArdioPulmonary bioImage Study (SCAPIS). After adjusting for multiple comparisons, we identified 1,008 associations between species alpha diversity and plasma metabolites, and 318,944 associations between specific gut metagenomic species and plasma metabolites. The gut microbiota explained up to 50% of the variance of individual plasma metabolites (mean of 4.7%). We present all results as the searchable association atlas "GUTSY" as a rich resource for mining associations, and exemplify the potential of the atlas by presenting novel associations between oral medication and the gut microbiome, and microbiota species strongly associated with levels of the uremic toxin p-cresol sulfate. The association atlas can be used as the basis for targeted studies of perturbation of specific bacteria and for identification of candidate plasma biomarkers of gut flora composition.


2021 ◽  
Vol 9 (9) ◽  
pp. 2002
Author(s):  
Chang Eon Park ◽  
Bum-Joon Cho ◽  
Min-Ji Kim ◽  
Hee Cheon Park ◽  
Jae-Ho Shin

The long-tailed goral (Naemorhedus caudatus) is an endangered species found in the mountains of eastern and northern Asia. Its populations have declined for various reasons, and this species has been designated as legally protected in South Korea. Although various ecological studies have been conducted on long-tailed gorals, none have investigated the gut microbiome until now. In the present study, we compared the diversity and composition of the gut microbiome of seven populations of Korean long-tailed gorals. By analyzing the gut microbiome composition for each regional population, it was found that four phyla—Firmicutes, Actinobacteriota, Bacteroidota, and Proteobacteria—were the most dominant in all regions on average. The alpha diversity of the gut microbiome of the goral population in the northern regions was high, while that in the southern regions was low. Through the analysis of beta diversity, the seven long-tailed goral populations have been divided into three groups: the Seoraksan population, the Samcheock population, and the Wangpicheon population. It was possible to confirm the regional migration of the animals using the gut microbiome based on the site-relational network analysis. It was found that the most stable population of long-tailed gorals in Korea was the Seoraksan population, and the closely related groups were the Samcheok and Wangpicheon populations, respectively. Wangpicheon appeared to be a major point of dispersal in the migration route of Korean long-tailed gorals.


2019 ◽  
Vol 10 (3) ◽  
pp. 265-278 ◽  
Author(s):  
V. Stadlbauer ◽  
A. Horvath ◽  
I. Komarova ◽  
B. Schmerboeck ◽  
N. Feldbacher ◽  
...  

The gut is hypothesised to play an important role in the development and progression of sepsis. It is however unknown whether the gut microbiome and the gut barrier function is already altered early in sepsis development and whether it is possible to modulate the microbiome in early sepsis. Therefore, a randomised, double blind, placebo-controlled pilot study to examine the alterations of the microbiome and the gut barrier in early sepsis and the influence of a concomitant probiotic intervention on dysbiosis at this early stage of the disease was conducted. Patients with early sepsis, defined as fulfilling the sepsis definition from the 2012 Surviving Sepsis Campaign guidelines but without signs of organ failure, received multispecies probiotic (Winclove 607 based on Omnibiotic® 10 AAD) for 28 days. Gut microbiome composition, function, gut barrier and bacterial translocation were studied. Patients with early sepsis had a significantly lower structural and functional alpha diversity, clustered differently and showed structural alterations on all taxonomic levels. Gut permeability was unaltered but endotoxin, endotoxin binding proteins and peptidoglycans were elevated in early sepsis patients compared to controls. Probiotic intervention successfully increased probiotic strains in stool and led to an improvement of functional diversity. Microbiome composition and function are altered in early sepsis. Probiotic intervention successfully modulates the microbiome and is therefore a promising tool for early intervention in sepsis.


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