scholarly journals Effects of Prebiotic Supplement on Gut Microbiota, Drug Bioavailability and Adverse Effects in Patients with Colorectal Cancer at Different Primary Tumor Locations Receiving Chemotherapy: Study Protocol for a Randomized Clinical Trial

Author(s):  
Yanmin Li ◽  
Hong Cao ◽  
Bojian Fei ◽  
Chuanqing Bao ◽  
Jianmin Xu ◽  
...  

Abstract Background: The prevalence of colorectal cancer (CRC) worldwide is a huge challenge to human health. Primary tumor locations found to impact prognosisand response to therapy. The important role of gut microbiota in the progression and treatment of CRC has led to many attempts of alleviating chemotherapy-induced adverse effects using microecologics. However, the underlying mechanism of the difference in the prognosis of different primary tumor locations and the synergistic effect of prebiotics on chemotherapy need to be further elucidated. This study aims to explore the differences in tumor microbiota and examine the effectiveness of xylooligosaccharides (XOS) on gut microbiota, adverse effects, and bioavailability of chemotherapy drugs in CRC patients at different primary tumor locations.Methods: This is a double-blinded, randomized, parallel controlled clinical trial. Participants with left-sided CRC (LSCRC, n = 50) and right-sided CC (RSCC, n = 50) will randomly allocated to prebiotic group (n = 25) or control group (n = 25) and will receive either a daily XOS (3 g/d) or placebo, respectively, for 12 weeks. The primary outcomes will be the differences in the mucosa microbiota composition at different tumor locations, and differences in gut microbiota composition, adverse effects, and blood concentration of capecitabine posttreatment. The secondary outcomes will include other blood indicators, short-chain fatty acids (SCFAs) concentration, quality of life, and mental health.Discussion: This study will reveal the potential benefits of prebiotic for improving the gut microbiota composition, alleviating the adverse effects, and improving the efficacy of chemotherapy in patients with CRC. In addition, this study will provide data on the different distribution of tumor microbiota and the different changes of gut microbiota during treatment in LSCRC and RSCC, which may provide novel insights into personalized cancer treatment strategies based on primary tumor locations and gut microbiota in the future.Trial registration: Chinese Clinical Trial Registry(www.chictr.org.cn): ChiCTR2100046237. Registered on 12 May 2021.

Author(s):  
Sofia Ainonen ◽  
Mysore V Tejesvi ◽  
Md. Rayhan Mahmud ◽  
Niko Paalanne ◽  
Tytti Pokka ◽  
...  

Abstract Background Intrapartum antibiotic prophylaxis (IAP) is widely used, but the evidence of the long-term effects on the gut microbiota and subsequent health of children is limited. Here, we compared the impacts of perinatal antibiotic exposure and later courses of antibiotic courses on gut microbiota. Methods This was a prospective, controlled cohort study among 100 vaginally delivered infants with different perinatal antibiotic exposures: control (27), IAP (27), postnatal antibiotics (24), and IAP and postnatal antibiotics (22). At 1 year of age, we performed next-generation sequencing of the bacterial 16S ribosomal RNA gene of fecal samples. Results Exposure to the perinatal antibiotics had a clear impact on the gut microbiota. The abundance of the Bacteroidetes phylum was significantly higher in the control group, whereas the relative abundance of Escherichia coli was significantly lower in the control group. The impact of the perinatal antibiotics on the gut microbiota composition was greater than exposure to later courses of antibiotics (28% of participants). Conclusions Perinatal antibiotic exposure had a marked impact on the gut microbiota at the age of 1 year. The timing of the antibiotic exposure appears to be the critical factor for the changes observed in the gut microbiota. Impact Infants are commonly exposed to IAP and postnatal antibiotics, and later to courses of antibiotics during the first year of life. Perinatal antibiotics have been associated with an altered gut microbiota during the first months of life, whereas the evidence regarding the long-term impact is more limited. Perinatal antibiotic exposure had a marked impact on the infant’s gut microbiota at 1 year of age. Impact of the perinatal antibiotics on the gut microbiota composition was greater than that of the later courses of antibiotics at the age of 1 year.


2021 ◽  
Vol 36 (Supplement_1) ◽  
Author(s):  
Renata Rodrigues Teixeira ◽  
Laila S. Andrade ◽  
Natalia Barros Ferreira Pereira ◽  
Christian Hoffmann ◽  
Lilian Cuppari

Abstract Background and Aims According to some studies, it seems that advanced chronic kidney disease (CKD) has the potential to cause alterations in the composition of patients gut microbiota. Most of these data have been provided by comparing the microbiota profile between patients and healthy individuals. However, well-known factors that influence the microbiota composition such as age, environment and diet were not considered in the majority of these comparative studies. In the present study, we aimed to compare the gut microbiota composition between patients on peritoneal dialysis (PD) and age-paired healthy household contacts. Method This is a cross-sectional study. Patients undergoing automated PD for at least 3 months, aged 18 to 75 years and clinically stable were enrolled. Those who were using prebiotics, probiotics, symbiotics and antibiotics within a period of 30 days before the study, were not included. A healthy control group was composed by individuals living in the same home and with similar age of the patients. Participants received sterile materials to collect the feces sample and were instructed to keep it refrigerated and bring to the clinic within a period of 12h. To evaluate the microbial profile, 16S ribosomal DNA was PCR-amplified and sequenced on an IlluminaMiSeq platform. Diet was evaluated using a 3-day food record and the diet quality was analyzed by a Brazilian Diet Quality Index. Rome IV questionnaire was applied to diagnose constipation. Nutritional status was assessed by 7-point subjective global assessment (SGA) and body mass index (BMI). Fasting blood samples were collected and clinical data were obtained from interviewing the participants and from the patient’s charts. Data are presented in percentage, mean ± standard deviation or median (interquartile range). Results Twenty patients (PD group) and 20 healthy household contacts (control group) were studied. In PD group: 70% were men, 53.5 (48.2 - 66) years old, 50% had diabetes, BMI 25.9 ± 4.8 kg/m², 95% well-nourished, 40% constipated, 14 (5.2 – 43.5) months on dialysis and 80% had residual diuresis. In control group: 30% were men, 51.5 (46.2 - 59.7) years old, BMI 28.7 ± 3.5 kg/m² and 20% constipated. Except of sex (p = 0.01) and BMI (p = 0.04), there were no other differences between groups. Comparing dietary intake between groups, no difference was found in daily energy [PD: 20.8 ± 5.4 kcal/kg/d vs. control: 22.0 ± 5.6 kcal/kg/d, p = 0.51], protein (PD: 0.8 ± 0.2 g/kg/d vs. control: 0.9 ± 0.2 g/kg/d, p = 0.23) and fiber [PD: 14.1 (10.7 – 21.1) g/d vs. 13.7 (10.4 – 18.0) g/d, p = 0.85]. In addition, the Diet Quality Index was also not different between groups (PD: 52.3 ± 15.6 vs. control: 54.5 ± 14.8, p = 0.65). Regarding microbiota composition, no difference was found between groups in alfa diversity (Figure 1), beta diversity (p>0.05), and genera differential abundance (Figure 2). Conclusion In the present study, no difference in the gut microbiota composition was found between patients on PD and healthy household contacts sharing a similar environment and diet. This result suggests that CKD and PD seem not to alter significantly gut microbiota composition.


2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Martin Iain Bahl ◽  
Anabelle Legarth Honoré ◽  
Sanne Tygesen Skønager ◽  
Oliver Legarth Honoré ◽  
Tove Clausen ◽  
...  

AbstractOn many mink farms, antibiotics are used extensively during the lactation period to reduce the prevalence and severity of pre-weaning diarrhoea (PWD) in mink kits (also referred to as greasy kit syndrome). Concerns have been raised, that routine treatment of PWD with antibiotics could affect the natural successional development of the gut microbiota, which may have long lasting consequences. Here we investigated the effects of early life antibiotic treatment administered for 1 week (postnatal days 13–20). Two routes of antibiotic administration were compared to a non-treated control group (CTR, n = 24). Routes of administration included indirect treatment, through the milk from dams receiving antibiotics by intramuscular administration (ABX_D, n = 24) and direct treatment by intramuscular administration to the kits (ABX_K, n = 24). A tendency for slightly increased weight at termination (Day 205) was observed in the ABX_K group. The gut microbiota composition was profiled by 16S rRNA gene sequencing at eight time points between Day 7 and Day 205. A clear successional development of the gut microbiota composition was observed and both treatment regimens caused detectable changes in the gut microbiota until at least eight days after treatment ceased. At termination, a significant positive correlation was identified between microbial diversity and animal weight.


2018 ◽  
Vol 120 (9) ◽  
pp. 1014-1022 ◽  
Author(s):  
Daniel Lin ◽  
Brandilyn A. Peters ◽  
Charles Friedlander ◽  
Hal J. Freiman ◽  
James J. Goedert ◽  
...  

AbstractIncreasing evidence indicates that gut microbiota may influence colorectal cancer risk. Diet, particularly fibre intake, may modify gut microbiota composition, which may affect cancer risk. We investigated the relationship between dietary fibre intake and gut microbiota in adults. Using 16S rRNA gene sequencing, we assessed gut microbiota in faecal samples from 151 adults in two independent study populations: National Cancer Institute (NCI), n 75, and New York University (NYU), n 76. We calculated energy-adjusted fibre intake based on FFQ. For each study population with adjustment for age, sex, race, BMI and smoking, we evaluated the relationship between fibre intake and gut microbiota community composition and taxon abundance. Total fibre intake was significantly associated with overall microbial community composition in NYU (P=0·008) but not in NCI (P=0·81). In a meta-analysis of both study populations, higher fibre intake tended to be associated with genera of class Clostridia, including higher abundance of SMB53 (fold change (FC)=1·04, P=0·04), Lachnospira (FC=1·03, P=0·05) and Faecalibacterium (FC=1·03, P=0·06), and lower abundance of Actinomyces (FC=0·95, P=0·002), Odoribacter (FC=0·95, P=0·03) and Oscillospira (FC=0·96, P=0·06). A species-level meta-analysis showed that higher fibre intake was marginally associated with greater abundance of Faecalibacterium prausnitzii (FC=1·03, P=0·07) and lower abundance of Eubacterium dolichum (FC=0·96, P=0·04) and Bacteroides uniformis (FC=0·97, P=0·05). Thus, dietary fibre intake may impact gut microbiota composition, particularly class Clostridia, and may favour putatively beneficial bacteria such as F. prausnitzii. These findings warrant further understanding of diet–microbiota relationships for future development of colorectal cancer prevention strategies.


2019 ◽  
Vol 180 (3) ◽  
pp. 165-176 ◽  
Author(s):  
Hanieh-Sadat Ejtahed ◽  
Raul Y Tito ◽  
Seyed-Davar Siadat ◽  
Shirin Hasani-Ranjbar ◽  
Zahra Hoseini-Tavassol ◽  
...  

Objective The increasing prevalence of obesity over the past few decades constitutes a global health challenge. Pharmacological therapy is recommended to accompany life-style modification for obesity management. Here, we perform a clinical trial to investigate the effects of metformin on anthropometric indices and gut microbiota composition in non-diabetic, treatment-naive obese women with a low-calorie diet (LCD). Design Randomized double-blind parallel-group clinical trial Methods Forty-six obese women were randomly assigned to the metformin (500 mg/tab) or placebo groups using computer-generated random numbers. Subjects in both groups took two tablets per day for 2 months. Anthropometric measurements and collection of blood and fecal samples were done at the baseline and at the end of the trial. Gut microbiota composition was assessed using 16S rRNA amplicon sequencing. Results Twenty-four and twenty-two subjects were included in the metformin + LCD and placebo + LCD groups, respectively; at the end of trial, 20 and 16 subjects were analyzed. The metformin + LCD and placebo + LCD caused a 4.5 and 2.6% decrease in BMI from the baseline values, respectively (P < 0.01). Insulin concentration decreased in the metformin + LCD group (P = 0.046). The overall fecal microbiota composition and diversity were unaffected in the metformin + LCD group. However, a significant specific increase in Escherichia/Shigella abundance was observed after metformin + LCD intervention (P = 0.026). Fecal acetate concentration, but not producers, was significantly higher in the placebo + LCD group, adjusted for baseline values and BMI (P = 0.002). Conclusions Despite the weight reduction after metformin intake, the overall fecal microbiota composition remained largely unchanged in obese women, with exception of changes in specific proteobacterial groups.


Genes ◽  
2019 ◽  
Vol 10 (4) ◽  
pp. 270 ◽  
Author(s):  
Ce Yuan ◽  
Clifford J. Steer ◽  
Subbaya Subramanian

Changes in gut microbiota composition have consistently been observed in patients with colorectal cancer (CRC). Yet, it is not entirely clear how the gut microbiota interacts with tumor cells. We know that tumor cells undergo a drastic change in energy metabolism, mediated by microRNAs (miRNAs), and that tumor-derived miRNAs affect the stromal and immune cell fractions of the tumor microenvironment. Recent studies suggest that host intestinal miRNAs can also affect the growth and composition of the gut microbiota. Our previous CRC studies showed a high-level of interconnectedness between host miRNAs and their microbiota. Considering all the evidence to date, we postulate that the altered nutrient composition and miRNA expression in the CRC microenvironment selectively exerts pressure on the surrounding microbiota, leading to alterations in its composition. In this review article, we present our current understanding of the role of miRNAs in mediating host–microbiota interactions in CRC.


Molecules ◽  
2018 ◽  
Vol 23 (11) ◽  
pp. 2832 ◽  
Author(s):  
Dan Cheng ◽  
Hongsheng Chang ◽  
Suya Ma ◽  
Jian Guo ◽  
Gaimei She ◽  
...  

Tiansi Liquid is a traditional Chinese herbal medicine used to treat depression; however, the underlying mechanisms remain unclear. Here, we examined the effect of Tiansi Liquid in a rat model of hydrocortisone-induced depression using behavioral testing, 16S rRNA high-throughput pyrosequencing and high-performance liquid chromatography-mass spectrometry-based metabolomics of the tryptophan (TRP)–kynurenine (KYN) pathway. Tiansi Liquid significantly improved the sucrose preference and exploratory behavior of the depressive rats. The richness of intestinal mucosa samples from the model (depressive) group tended to be higher than that from the control group, while the richness was higher in the Tiansi Liquid-treated group than in the model group. Tiansi Liquid increased the relative abundance of some microbiota (Ruminococcaceae, Lactococcus, Lactobacillus, Lachnospiraceae_NK4A136_group). Metabolomics showed that Tiansi Liquid reduced the levels of tryptophan 2,3 dioxygenase, indoleamine 2,3-dioxygenase, quinoline and the KYN/TRP ratio, while increasing kynurenic acid and 5-HT levels. Correlation analysis revealed a negative relationship between the relative abundance of the Lachnospiraceae_NK4A136_group and quinoline content. Collectively, these findings suggest that Tiansi Liquid ameliorates depressive symptoms in rats by modulating the gut microbiota composition and metabolites in the TRP–KYN pathway.


2015 ◽  
Vol 113 (5) ◽  
pp. 728-738 ◽  
Author(s):  
Tatiana M. Marques ◽  
Rebecca Wall ◽  
Orla O'Sullivan ◽  
Gerald F. Fitzgerald ◽  
Fergus Shanahan ◽  
...  

The main aim of the present study was to investigate the effects of dietary trans-10, cis-12-conjugated linoleic acid (t10c12-CLA) on intestinal microbiota composition and SCFA production. C57BL/6 mice (n 8 per group) were fed a standard diet either supplemented with t10c12-CLA (0·5 %, w/w) (intervention) or with no supplementation (control), daily for 8 weeks. Metabolic markers (serum glucose, leptin, insulin and TAG, and liver TAG) were assessed by ELISA commercial kits, tissue long-chain fatty acids and caecal SCFA by GC, and microbial composition by 16S rRNA pyrosequencing. Dietary t10c12-CLA significantly decreased visceral fat mass (P< 0·001), but did not affect body weight (intervention), when compared with no supplementation (control). Additionally, lipid mass and composition were affected by t10c12-CLA intake. Caecal acetate, propionate and isobutyrate concentrations were higher (P< 0·05) in the t10c12-CLA-supplemented group than in the control group. The analysis of the microbiota composition following 8 weeks of t10c12-CLA supplementation revealed lower proportions of Firmicutes (P= 0·003) and higher proportions of Bacteroidetes (P= 0·027) compared with no supplementation. Furthermore, t10c12-CLA supplementation for 8 weeks significantly altered the gut microbiota composition, harbouring higher proportions of Bacteroidetes, including Porphyromonadaceae bacteria previously linked with negative effects on lipid metabolism and induction of hepatic steatosis. These results indicate that the mechanism of dietary t10c12-CLA on lipid metabolism in mice may be, at least, partially mediated by alterations in gut microbiota composition and functionality.


2017 ◽  
Author(s):  
Anhua Wu ◽  
Juping Duan ◽  
Sidi Liu ◽  
Xiujuan Meng ◽  
Pengcheng Zhou ◽  
...  

AbstractBackgroundGut microbiota composition of intensive care unit (ICU) patients suffering from Clostridium difficile-positive diarrhea (CDpD) is still poorly understood. This study aims to use 16S rDNA (and metagenome) sequencing to compare the microbiota composition of 58 (and 5) ICU patients with CDpD (CDpD group), 33 (and 4) ICU patients with C. difficile negative diarrhea (CDnD group), and 21 (and 5) healthy control subjects (control group), as well as CDpD patients in A+B+ (N=34; A/B: C. difficile TcdA/B), A-B+ (N=7), and A-B- (N=17) subgroups. For 16S rDNA data, OTU clustering (tool: UPARSE), taxonomic assignment (tool: RDP classifier), α-diversity and β-diversity analyses (tool: QIIME) were conducted. For metagenome data, metagenome assembly (tool: SOAP), gene calling (tools: MetaGeneMark, CD-HIT, and SoapAligner), unigene alignment (tool: DIAMOND), taxon difference analysis (tool: Metastats), and gene annotation (tool: DIAMOND) were performed.ResultsThe microbial diversity of CDpD group was lower than that of CDnD and control groups. The abundances of 10 taxa (e.g. Deferribacteres, Cryptomycota, Acetothermia) in CDpD group were significantly higher than that in CDnD group. The abundances of Saccharomycetes and Clostridia were significantly lower in CDpD in comparison with control. A+B+, A-B+ and A-B- subgroups couldn’t be separated in principal component analysis, while some taxa are significantly different between A+B+ and A-B- subgroups.ConclusionCDpD might relate to the decrease of beneficial taxa (i.e. Saccharomycetes and Clostridia) and the increase of harmful taxa (e.g. Deferribacteres, Cryptomycota, Acetothermia) in gut microbiota in ICU patients. C. difficile type might be slightly associated with gut microbiota composition.


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