scholarly journals Impact of investigational microbiota therapeutic RBX2660 on the gut microbiome and resistome revealed by a placebo-controlled clinical trial

2020 ◽  
Author(s):  
Suryang Kwak ◽  
JooHee Choi ◽  
Tiffany Hink ◽  
Kimberly A. Reske ◽  
Kenneth Blount ◽  
...  
Keyword(s):  
Relative Abundance ◽  
Gut Microbiome ◽  
Post Treatment ◽  
Patient Specific ◽  
Controlled Clinical Trial ◽  
Investigational Drug ◽  
Metagenomic Sequencing ◽  
Double Blind ◽  
Significant Recovery ◽  
Clostridioides Difficile

Abstract Background. Intestinal microbiota restoration can be achieved by complementing a subject’s perturbed microbiota with that of a healthy donor. Recurrent Clostridioides difficile infection (rCDI) is one key application of such treatment. Another emerging application of interest is reducing antibiotic resistant genes (ARGs) and organisms (AROs). In this study, we investigated fecal specimens from a multicenter, randomized, double-blind, placebo-controlled phase 2b study of microbiota-based investigational drug RBX2660. Patients were administered either placebo, 1 dose of RBX2660 and 1 placebo, or 2 doses of RBX2660 via enema and longitudinally tracked for changes in their microbiome and antibiotic resistome.Results. All patients exhibited significant recovery of gut microbiome diversity and a decrease of ARG relative abundance during the first 7 days post-treatment. However, the microbiome and resistome shifts towards average configurations from unperturbed individuals were more significant and longer-lasting in RBX2660 recipients compared to placebo. We quantified microbiome and resistome modification by RBX2660 using a novel ‘transplantation index’ metric. We identified taxonomic and metabolic features distinguishing the baseline microbiome of non-transplanted patients and taxa specifically enriched during the process of transplantation. We elucidated the correlation between resistome and taxonomic transplantations and post-treatment dynamics of patient-specific and RBX2660-specific ARGs. Whole genome sequencing of AROs cultured from RBX2660 product and patient samples indicate ARO eradication in patients via RBX2660 administration, but also, to a lesser extent, introduction of RBX2660-derived AROs.Conclusions. Through shotgun metagenomic sequencing, we elucidated the effects of RBX2660 in the microbiome and resistome. Antibiotic discontinuation alone resulted in significant recovery of gut microbial diversity and reduced ARG relative abundance, but RBX2660 administration more rapidly and completely changed the composition of patients’ microbiome, resistome, and ARO colonization by transplanting RBX2660 microbiota into the recipients. Although ARGs and AROs were transmitted through RBX2660, the resistome post-RBX2660 more closely resembled that of the administered product—a proxy for the donor—than an antibiotic perturbed state.Trial registration: NCT02299570. Registered 19 November 2014, https://clinicaltrials.gov/ct2/show/NCT02299570

scholarly journals The effect of microbiota-based investigational drug RBX2660 on the gut microbiome and resistome revealed by a placebo-controlled clinical trial

2020 ◽  
Author(s):  
Suryang Kwak ◽  
JooHee Choi ◽  
Tiffany Hink ◽  
Kimberly A. Reske ◽  
Kenneth Blount ◽  
...  
Keyword(s):  
Gut Microbiome ◽  
Post Treatment ◽  
Patient Specific ◽  
Controlled Clinical Trial ◽  
Investigational Drug ◽  
Metagenomic Sequencing ◽  
Double Blind ◽  
Significant Recovery ◽  
Clostridioides Difficile ◽  
Shotgun Metagenomic Sequencing

Abstract Background. Intestinal microbiota restoration can be achieved by replacing a subject’s perturbed microbiota with that of a healthy donor. Recurrent Clostridioides difficile infection (rCDI) is one key application of such treatment. Another emerging application of interest is depletion of antibiotic resistant genes (ARGs) and organisms (AROs). In this study, we investigated fecal specimens from a multicenter, randomized, double-blind, placebo-controlled phase 2b study of microbiota-based investigational drug RBX2660. Patients were administered either placebo, 1 dose of RBX2660 and 1 placebo, or 2 doses of RBX2660 via enema and longitudinally tracked for changes in their microbiome and antibiotic resistome. Results. All patients exhibited significant recovery of gut microbiome diversity and a decrease of ARG abundance during the first 7 days post-treatment. However, the microbiome and resistome shifts towards healthier configurations were more significant and longer-lasting in RBX2660 recipients compared to placebo. We quantified microbiome and resistome modification by RBX2660 using a novel ‘transplantation index’ metric. We identified taxonomic and metabolic features distinguishing the baseline microbiome of non-transplanted patients and taxa specifically enriched during the process of transplantation. We elucidated the correlation between resistome and taxonomic transplantations and post-treatment dynamics of patient-specific and RBX2660-specific ARGs. Whole genome sequencing of AROs cultured from RBX2660 product and patient samples indicate ARO eradication in patients via RBX2660 administration, but also, to a lesser extent, introduction of RBX2660-derived AROs. Conclusions. Through shotgun metagenomic sequencing, we elucidated the effects of RBX2660 in the microbiome and resistome. Antibiotic discontinuation alone resulted in significant recovery of gut microbial diversity and reduced ARG abundance, but RBX2660 administration more rapidly and completely changed the composition of patients’ microbiome, resistome, and ARO colonization by transplanting RBX2660 microbiota into the recipients. Although ARGs and AROs were transmitted through RBX2660, the resistome post-RBX2660 more closely resembled that of the administered product—a proxy for the donor—than an antibiotic perturbed state.

scholarly journals The effect of microbiota-based investigational drug RBX2660 on the gut microbiome and resistome revealed by a placebo-controlled clinical trial

2020 ◽  
Author(s):  
Suryang Kwak ◽  
JooHee Choi ◽  
Tiffany Hink ◽  
Kimberly A. Reske ◽  
Kenneth Blount ◽  
...  
Keyword(s):  
Gut Microbiome ◽  
Post Treatment ◽  
Patient Specific ◽  
Controlled Clinical Trial ◽  
Investigational Drug ◽  
Double Blind ◽  
Significant Recovery ◽  
Clostridioides Difficile ◽  
Metabolic Functions ◽  
Clostridioides Difficile Infection

Abstract Background Intestinal microbiota restoration can be achieved by replacing a subject’s perturbed microbiota with that of a healthy donor. Recurrent Clostridioides difficile infection (rCDI) is one key application of such treatment. Another application of interest is depletion of antibiotic resistant genes (ARGs) and organisms (AROs). In this study, we investigated fecal specimens from a multicenter, randomized, double-blind, placebo-controlled phase 2b study of microbiota-based investigational drug RBX2660. Patients were administered either placebo, 1 dose of RBX2660 and 1 placebo, or 2 doses of RBX2660 via enema and longitudinally tracked for changes in their microbiome and antibiotic resistome. Results All patients exhibited significant recovery of gut microbiome diversity and decrease of ARG abundance during the first 7 days post-treatment. However, the microbiome and resistome shifts towards healthier configurations were more significant and longer lasting in RBX2660 recipients compared to placebo. We identified 18 taxa and 21 metabolic functions distinguishing the baseline microbiome of non-transplanted patients, and the majority of features were correlated to intrinsic vancomycin resistance. We also identified 7 patient-specific and 3 RBX2660-specific ARGs and tracked their dynamics post treatment. Whole genome sequencing of AROs cultured from RBX2660 product and patient samples indicate ARO eradication in patients via RBX2660 administration, but also, to a lesser extent, introduction of RBX2660-derived AROs. Conclusions By including a placebo group, we distinguished the effects of RBX2660 from baseline post-antibiotic microbiome dynamics. Antibiotic discontinuation alone resulted in significant recovery of gut microbial diversity and reduced ARG abundance, but RBX2660 administration more rapidly and completely changed the composition of patients’ microbiome, resistome, and ARO colonization by transplanting RBX2660 microbiota into the recipients. Although ARGs and AROs were transmitted through RBX2660, the resistome post-RBX2660 more closely resembled that of the administered product—a proxy for the donor—than an antibiotic perturbed state.

scholarly journals The Infant Gut Resistome is Associated with E. coli and Early-life Exposures

2020 ◽  
Author(s):  
Rebecca M. Lebeaux ◽  
Modupe O. Coker ◽  
Erika F. Dade ◽  
Thomas J. Palys ◽  
Hilary G. Morrison ◽  
...  
Keyword(s):  
Antibiotic Resistance ◽  
Relative Risk ◽  
Relative Abundance ◽  
Gut Microbiome ◽  
Early Life ◽  
The United States ◽  
Delivery Mode ◽  
Metagenomic Sequencing ◽  
E Coli ◽  
Early Life Exposures

Abstract Background: Antibiotic resistance is an increasing threat to human health. The human gut microbiome harbors a collection of bacterial antimicrobial resistance genes (ARGs) known as the resistome. The factors associated with establishment of the resistome in early life are not well understood and clarifying these factors would inform strategies to decrease antibiotic resistance. We investigated the early-life exposures and taxonomic signatures associated with resistome development over the first year of life in a large, prospective cohort in the United States. Shotgun metagenomic sequencing was used to profile both microbial composition and ARGs in stool samples collected at 6 weeks and 1 year of age from infants enrolled in the New Hampshire Birth Cohort Study. Negative binomial regression and statistical modeling was used to examine infant factors such as sex, delivery mode, feeding method, gestational age, antibiotic exposure, and infant gut microbiome composition in relation to the diversity and relative abundance of ARGs.Results: Metagenomic sequencing was performed on paired samples from 195 full term (at least 37 weeks’ gestation) and 15 late preterm (33-36 weeks’ gestation) infants. 6-week samples compared to 1-year samples had 4.37 times (95% CI: 3.54-5.39) the rate of harboring ARGs. The majority of ARGs that were at a greater relative abundance at 6 weeks (chi-squared p < 0.01) worked through the mechanism of antibiotic efflux (i.e., by pumping antibiotics out of the cell). The overall relative abundance of the resistome was strongly correlated with Proteobacteria (Spearman correlation = 78.9%) and specifically E. coli (62.2%) relative abundance in the gut microbiome. Among infant characteristics, delivery mode was most strongly associated with the diversity and relative abundance of ARGs. Infants born via cesarean delivery had a higher risk of harboring unique ARGs [relative risk = 1.12 (95% CI: 0.97 – 1.29)] as well as a having an increased risk for overall ARG relative abundance [relative risk = 1.43 (95% CI: 1.12 – 1.84)] at 1 year compared to infants born vaginally. Additionally, 6 specific ARGs were at a greater relative abundance in infants delivered by cesarean section compared to vaginally delivered infants across both time points. Conclusions: Our findings suggest that the developing infant gut resistome may be alterable by early-life exposures. Establishing the extent to which infant characteristics and early-life exposures impact the resistome can ultimately lead to interventions that decrease the transmission of ARGs and thus the possibility of antibiotic resistant life threatening infections.

scholarly journals Weaning age and its effect on the development of the swine gut microbiome and resistome

2021 ◽  
Author(s):  
Devin B Holman ◽  
Katherine E Gzyl ◽  
Kathy T Mou ◽  
Heather K Allen
Keyword(s):  
Relative Abundance ◽  
Gut Microbiome ◽  
Rrna Gene ◽  
Metagenomic Sequencing ◽  
Carbohydrate Active Enzymes ◽  
Fecal Microbiome ◽  
Shotgun Metagenomic Sequencing ◽  
Swine Operations ◽  
Weaning Age

Piglets are often weaned between 19 and 22 d of age in North America although in some swine operations this may occur at 14 d or less. Piglets are abruptly separated from their sow at weaning and are quickly transitioned from sow's milk to a plant-based diet. The effect of weaning age on the long-term development of the pig gut microbiome is largely unknown. In this study, pigs were weaned at either 14, 21, or 28 d of age and fecal samples collected 21 times from d 4 (neonatal) through to marketing at d 140. The fecal microbiome was characterized using 16S rRNA gene and shotgun metagenomic sequencing. The fecal microbiome of all piglets shifted significantly three to seven days post-weaning with an increase in microbial diversity. Several Prevotella spp. increased in relative abundance immediately after weaning as did butyrate-producing species such as Butyricicoccus porcorum, Faecalibacterium prausnitzii, and Megasphaera elsdenii. Within 7 days of weaning, the gut microbiome of pigs weaned at 21 and 28 days of age resembled that of pigs weaned at 14 d. Resistance genes to most antimicrobial classes decreased in relative abundance post-weaning with the exception of those conferring resistance to tetracyclines and macrolides-lincosamides-streptogramin B. The relative abundance of microbial carbohydrate-active enzymes (CAZymes) changed significantly in the post-weaning period with an enrichment of CAZymes involved in degradation of plant-derived polysaccharides. These results demonstrate that pigs tend to have a more similar microbiome as they age and that weaning age has only a temporary effect on the gut microbiome.

scholarly journals Identification and engraftment of new bacterial strains by shotgun metagenomic sequence analysis in patients with recurrent Clostridioides difficile infection before and after fecal microbiota transplantation and in healthy human subjects

PLoS ONE ◽  
2021 ◽  
Vol 16 (7) ◽  
pp. e0251590
Author(s):  
Sandeep Verma ◽  
Sudhir K. Dutta ◽  
Elad Firnberg ◽  
Laila Phillips ◽  
Rakesh Vinayek ◽  
...  
Keyword(s):  
Relative Abundance ◽  
Fecal Microbiota Transplantation ◽  
Bacterial Species ◽  
Fecal Microbiota ◽  
Metagenomic Sequencing ◽  
Bacterial Strains ◽  
Metagenomic Sequence ◽  
Clostridioides Difficile ◽  
Healthy Donors ◽  
Before And After

Background Recurrent Clostridioides diffícile infection (RCDI) is associated with major bacterial dysbiosis and colitis. Fecal microbiota transplantation (FMT) is a highly effective therapeutic modality for RCDI. While several studies have identified bacterial species associated with resolution of symptoms in patients, characterization of the fecal microbiome at the bacterial strain level in RCDI patients before and after FMT and healthy donors, has been lacking. The aim of this study was to examine the ability of bacterial strains from healthy donors to engraft in the gastrointestinal tract of patients with RCDI following FMT. Methods Fecal samples were collected from 22 patients with RCDI before and after FMT and their corresponding healthy donors. Total DNA was extracted from each sample and analyzed by shotgun metagenomic sequencing. The Cosmos-ID analysis platform was used for taxonomic assignment of sequences and calculation of the relative abundance (RA) of bacterial species and strains. From these data, the total number of bacterial strains (BSI), Shannon diversity index, dysbiosis index (DI), and bacterial engraftment factor, were calculated for each strain. Findings A marked reduction (p<0·0001) in the RA of total and specific bacterial strains, especially from phylum Firmicutes, was observed in RCDI patients prior to FMT. This change was associated with an increase in the DI (p<0·0001) and in pathobiont bacterial strains from phylum Proteobacteria, such as Escherichia coli O157:H7 and Klebsiella pneumoniae UCI 34. BSI was significantly lower in this group of patients as compared to healthy donors and correlated with the Shannon Index. (p<0·0001). Identification and engraftment of bacterial strains from healthy donors revealed a greater diversity and higher relative abundance of short-chain fatty acid (SCFA)-producing bacterial strains, including Lachnospiraceae bacterium 5_1_63FAA_u_t, Dorea formicigenerans ATCC 27755, Anaerostipes hadrusand others, in RCDI patients after FMT. Interpretation These observations identify a group of SCFA-producing bacterial strains from healthy donors that engraft well in patients with RCDI following FMT and are associated with complete resolution of clinical symptoms and bacterial dysbiosis.

scholarly journals The effect of legume supplementation on the gut microbiota in rural Malawian infants aged 6 to 12 months

2020 ◽  
Vol 111 (4) ◽  
pp. 884-892
Author(s):  
M Isabel Ordiz ◽  
Stefan Janssen ◽  
Greg Humphrey ◽  
Gail Ackermann ◽  
Kevin Stephenson ◽  
...  
Keyword(s):  
Common Bean ◽  
Intestinal Permeability ◽  
Relative Abundance ◽  
Linear Growth ◽  
Fecal Microbiota ◽  
Sub Saharan Africa ◽  
Controlled Clinical Trial ◽  
Double Blind ◽  
Fecal Microbiome ◽  
Α Diversity

ABSTRACT Background Common bean and cowpea contain about 25% protein and 25% fiber, and are recommended as complementary foods in sub-Saharan Africa. Objective The objective of this study was to determine if a daily legume supplement given to Malawian infants aged 6 to 12 mo alters the 16S configuration of the fecal microbiota as read out by amplicon sequence variants (ASVs). Methods This study was conducted within the context of a randomized, double-blind, controlled clinical trial to assess whether cowpea or common bean supplementation reduced intestinal permeability or increased linear growth. There were 2 village clusters in which the study was conducted. Fresh stool collections were flash frozen from 236 infants at ≤6 time points. The stools were sequenced using Earth Microbiome project protocols and data were processed using Qiime and Qiita, open-source, validated software packages. α-diversity was measured using the Faith's test. The 16S configuration was characterized by determining the weighted UniFrac distances of the ASVs and comparing them using permutational multivariate ANOVA. Results Among the 1249 samples analyzed, the α-diversity of the fecal microbiome was unchanged among subjects after initiation of legume supplementation. Neither cowpea nor common bean altered the overall 16S configuration at any age. The 16S configuration differed between children with adequate and poor linear growth aged from 6 to 9 mo, but no specific ASVs differed in relative abundance. The 16S configuration differed between children with normal and abnormal intestinal permeability at 9 mo, but no specific ASVs differed in relative abundance. Among categorical characteristics of the population associated with different 16S configurations, village cluster was most pronounced. Conclusion Legume supplementation in breastfed, rural African infants did not affect the structure of the gut microbial communities until the children were aged 9 mo. This trial was registered at clinicaltrials.gov as NCT02472262.

scholarly journals Clinical efficacy of Tailin formulation combined with continuous low-dose antimicrobial therapy for recurrent urinary tract infection: study protocol for a multicenter, double-blind, randomized, controlled clinical trial

Trials ◽  
2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Tonglu Li ◽  
Yingru Xu ◽  
Xuezhong Gong
Keyword(s):  
Clinical Trial ◽  
Urinary Tract Infection ◽  
Urinary Tract ◽  
Tract Infection ◽  
Post Treatment ◽  
Controlled Clinical Trial ◽  
Double Blind ◽  
Randomized Controlled ◽  
Treatment Changes

Abstract Background Given the increasing rates of antimicrobial resistance (AMR), recurrent urinary tract infection (rUTI) is becoming refractory more and more. Antibiotic prophylaxis including continuous low-dose antibiotic therapy (CLAT), is the common treatment for rUTI of the world. However, the presumably adverse reactions caused by CLAT alone should be paid more attention. Studies indicated that Chinese herbal medicine (CHM) might be an available treatment method for rUTI. Tailin formulation (TLF) is a herbal prescription developed for the treatment of rUTI in the 2000s in Shanghai Municipal Hospital of Traditional Chinese Medicine. Our previous studies have shown TLF could prevent urinary tract infection both in pyelonephritis (PN) rat model and in PN patients. Additionally, our published data demonstrated TLF is helpful to reduce the recurrence of rUTI and protect renal tubular function in clinic. In order to find a novel treating project for rUTI to increase the clinical curative effect, we thus try to combine TLF with CLAT to treat rUTI and design an optimized, pragmatically clinical trial to evaluate the efficacy and safety of this project. Methods/design This is a multicenter, double-blind, randomized, controlled clinical trial. We will enroll 200 eligible patients diagnosed with uncomplicated rUTI and then divide them randomly into two groups with a 1:1 ratio: TLF + CLAT group and placebo + CLAT group. This trial consists of two stages, a 12-week period of treatment and a 12-week period of post-treatment follow-up, respectively. The primary outcome will be the recurrence rate at the 12th week of the follow-up period; the second outcomes will be the post-treatment changes in renal and liver function; furthermore, traditional Chinese medicine (TCM) symptoms, non-infection-related physical signs, and subjective symptoms will be scored, and the number of episodes of each subject will be also recorded; meanwhile, vital signs indicators and serious adverse events (SAEs) will be monitored throughout the trial. Discussion This study will provide convictive research-derived data to evaluate clinical efficacy and safety of TLF combined with CLAT for rUTI, and provide an evidence-based recommendation for clinicians. Moreover, post-treatment changes in non-infection-related physical signs and subjective symptoms were included in the efficacy evaluation, which is important and more significant for assessing the clinical benefits for those rUTI patients. Trial registration Chinese Clinical Trial Registry ChiCTR2100041914. Registered on 10 January 2021. Protocol date and version: September 12, 2020; version 1.

scholarly journals SER-109, an Investigational Microbiome Drug to Reduce Recurrence After Clostridioides difficile Infection: Lessons Learned From a Phase 2 Trial

2020 ◽  
Author(s):  
Barbara H McGovern ◽  
Christopher B Ford ◽  
Matthew R Henn ◽  
Darrell S Pardi ◽  
Sahil Khanna ◽  
...  
Keyword(s):  
Bile Acid ◽  
Statistical Significance ◽  
Standard Of Care ◽  
Lessons Learned ◽  
Metagenomic Sequencing ◽  
Double Blind ◽  
Secondary Bile Acid ◽  
Phase 2 Trial ◽  
Clostridioides Difficile ◽  
Clostridioides Difficile Infection

Abstract Background Recurrent Clostridioides difficile infection (rCDI) is associated with loss of microbial diversity and microbe-derived secondary bile acids, which inhibit C. difficile germination and growth. SER-109, an investigational microbiome drug of donor-derived, purified spores, reduced recurrence in a dose-ranging, phase (P) 1 study in subjects with multiple rCDIs. Methods In a P2 double-blind trial, subjects with clinical resolution on standard-of-care antibiotics were stratified by age (&lt; or ≥65 years) and randomized 2:1 to single-dose SER-109 or placebo. Subjects were diagnosed at study entry by PCR or toxin testing. Safety, C. difficile–positive diarrhea through week 8, SER-109 engraftment, and bile acid changes were assessed. Results 89 subjects enrolled (67% female; 80.9% diagnosed by PCR). rCDI rates were lower in the SER-109 arm than placebo (44.1% vs 53.3%) but did not meet statistical significance. In a preplanned analysis, rates were reduced among subjects ≥65 years (45.2% vs 80%, respectively; RR, 1.77; 95% CI, 1.11–2.81), while the &lt;65 group showed no benefit. Early engraftment of SER-109 was associated with nonrecurrence (P &lt; .05) and increased secondary bile acid concentrations (P &lt; .0001). Whole-metagenomic sequencing from this study and the P1 study revealed previously unappreciated dose-dependent engraftment kinetics and confirmed an association between early engraftment and nonrecurrence. Engraftment kinetics suggest that P2 dosing was suboptimal. Adverse events were generally mild to moderate in severity. Conclusions Early SER-109 engraftment was associated with reduced CDI recurrence and favorable safety was observed. A higher dose of SER-109 and requirements for toxin testing were implemented in the current P3 trial. Clinical Trials Registration NCT02437487, https://clinicaltrials.gov/ct2/show/NCT02437487?term=SER-109&draw= 2&rank=4.

scholarly journals Bioavailability of a Novel Form of Microencapsulated Bovine Lactoferrin and Its Effect on Inflammatory Markers and the Gut Microbiome: A Pilot Study

Nutrients ◽  
2018 ◽  
Vol 10 (8) ◽  
pp. 1115 ◽  
Author(s):  
Clare Dix ◽  
Olivia Wright
Keyword(s):  
Gut Microbiome ◽  
Bovine Lactoferrin ◽  
Metagenomic Sequencing ◽  
Serum Samples ◽  
Double Blind ◽  
16S Sequencing ◽  
Cd8 Cells ◽  
Beneficial Effects ◽  
Positive Effects ◽  
Before And After

Bovine lactoferrin, extracted from milk or whey, is used in a range of products to enhance immunity and support digestive health, iron absorption, and homeostasis. This study examined the absorption and effect of Progel (Brisbane, Queensland, Australia) microencapsulated bovine lactoferrin (InferrinTM, Bega Bionutrients, Victoria, Australia) on immune markers and the microbiome. A double-blind randomised, cross-over trial was conducted with 12 healthy males randomised to one of two doses, equivalent to 200 mg or 600 mg lactoferrin, for two four-week supplementation arms, with a two-week washout period. Subjects received either standard bovine lactoferrin or InferrinTM for each arm. Baseline and post each trial arm, CD69+ activation on CD4+ and CD8+ cells was analysed, bovine and human lactoferrin contents of faecal and serum samples were reported, and the gut microbiome was analysed using 16S sequencing and metagenomic sequencing. The mean level of CD69+ activation on the CD4+ cells was lower after supplementation regardless of the form or dose of lactoferrin. This was statistically significant for the 200 mg dose. A higher level of bovine lactoferrin was found post-supplementation in those taking InferrinTM, although this was not statistically significant. Changes in phylum-level microbial community profiling were detected post-supplementation in the second trial arm, particularly in those receiving InferrinTM. Metagenomic sequencing showed changes in the volumes of the top 100 species of bacteria present before and after all treatment arms. Results suggest that lactoferrin supplementation may have beneficial effects on the microbiome and immune system, and that the use of InferrinTM improves absorption. Larger detailed studies are needed to ascertain the potential positive effects of bovine lactoferrin supplementation.

scholarly journals Alterations, Interactions, and Diagnostic Potential of Gut Bacteria and Viruses in Colorectal Cancer

2021 ◽  
Vol 11 ◽  
Author(s):  
Renyuan Gao ◽  
Yefei Zhu ◽  
Cheng Kong ◽  
Kai Xia ◽  
Hao Li ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Relative Abundance ◽  
Gut Microbiome ◽  
Fusobacterium Nucleatum ◽  
Gut Bacteria ◽  
Microbial Interactions ◽  
Diagnostic Model ◽  
Metagenomic Sequencing ◽  
Diagnostic Potential ◽  
Diagnostic Panel

Gut microbiome alteration was closely associated with colorectal cancer (CRC). Previous studies had demonstrated the bacteria composition changes but lacked virome profiles, trans-kindom interactions, and reliable diagnostic model explorations in CRC. Hence, we performed metagenomic sequencing to investigate the gut microbiome and microbial interactions in adenoma and CRC patients. We found the decreased microbial diversity in CRC and revealed the taxonomic alterations of bacteria and viruses were highly associated with CRC at the species level. The relative abundance of oral-derived species, such as Fusobacterium nucleatum, Fusobacterium hwasookii, Porphyromonas gingivalis, and Bacteroides fragilis, increased. At the same time, butyrate-producing and anti-inflammatory microbes decreased in adenoma and CRC by non-parametric Kruskal-Wallis test. Despite that, the relative abundance of Escherichia viruses and Salmonella viruses increased, whereas some phages, including Enterobacteria phages and Uncultured crAssphage, decreased along with CRC development. Gut bacteria was negatively associated with viruses in CRC and healthy control by correlation analysis (P=0.017 and 0.002, respectively). Viruses were much more dynamic than the bacteria as the disease progressed, and the altered microbial interactions were distinctively stage-dependent. The degree centrality of microbial interactions decreased while closeness centrality increased along with the adenoma to cancer development. Uncultured crAssphage was the key bacteriophage that enriched in healthy controls and positively associated with butyrate-producing bacteria. Diagnostic tests based on bacteria by random forest confirmed in independent cohorts showed better performance than viruses for CRC. In conclusion, our study revealed the novel CRC-associated bacteria and viruses that exhibited specific differences and intensive microbial correlations, which provided a reliable diagnostic panel for CRC.

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