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Fecal microbiota transplantation (FMT) is an effective and safe treatment to treat recurrent Clostridioides difficile infection. It is essential to make every effort to perform FMT rigorously and based on scientific knowledge. Selection of the fecal microbiota donor is a key point of the process to ensure recipient safety. It is necessary to have protocols of action that allow clinicians to act with the maximum guarantees and to minimize the risks of the procedure. For this reason, a multidisciplinary working group has been set up in Cataluna with the aim of establishing recommendations for the selection of the fecal microbiota donor.

The inclusion of high-quality proteins are commonly used in swine production. Our research investigated the effects of hydrolyzed wheat protein (HWP), fermented soybean meal (FSBM), and enzyme-treated soybean meal (ESBM) on growth performance, antioxidant capacity, immunity, fecal microbiota and metabolites of weaned piglets. A total of 144 piglets (weaned at 28 d) were allotted to 3 dietary treatments with 6 replicate pens per treatment and 8 piglets per pen. This study included 2 periods: d 0 to14 for phase 1 and d 15 to 28 for phase 2. Dietary treatments contained 15.90% HWP, 15.80% FSBM, and 15.10% ESBM in phase 1, and 7.90% HWP, 7.80% FSBM, and 7.50% ESBM in phase 2, respectively. The ADG of piglets in ESBM was increased (P

Background Fecal microbiota transfer (FMT) has become a standard of care in the prevention of multiple recurrent Clostridioides difficile (rCDI) infection. Aim While primary cure rates range from 70–80% following a single treatment using monodirectional approaches, cure rates of combination treatment remain largely unknown. Methods In a retrospective case-control study, outcomes following simultaneous bidirectional FMT (bFMT) with combined endoscopic application into the upper and lower gastrointestinal tract, compared to standard routes of application (endoscopy via upper or lower gastrointestinal tract and oral capsules; abbreviated UGIT, LGIT and CAP) on day 30 and 90 after FMT were assessed. Statistical matching partners were identified using number of recurrences ( Results Primary cure rates at D30 and D90 for bFMT were 100% (p=.001). The matched control groups showed cure rates of 81.3% for LGIT (p=.010), 62.5% for UGIT (p=.000) and 78.1% for CAP (p=.005) on D30 and 81.3% for LGIT (p=.010), 59.4% for UGIT (p=.000) and 71.9% for CAP (p=.001) on D90. Conclusion In our analysis, bFMT on the same day significantly increased primary cure rate at D30 and D90. These data require prospective confirmation but suggest that route of application may play a significant role in optimizing patient outcomes. ClinicalTrials.gov no: NCT02681068

Regular almond consumption has been shown to improve body weight management, lipid profile and blood glucose control. We hypothesized that almond consumption would alter fecal microbiota composition, including increased abundance and activity of potentially beneficial bacterial taxa in adults who are overweight and obese with elevated fasting blood glucose. A total of 69 adults who were overweight or obese with an elevated plasma glucose (age: 60.8 ± 7.4, BMI ≥27 kg/m2, fasting plasma glucose ≥5.6 to

Research increasingly shows that the gut-liver-brain axis is a crucial component in the pathophysiology of hepatic encephalopathy (HE). Due to the limitations of current standard-of-care medications, non-pharmacological treatments that target gut dysbiosis, including probiotics, nutritional management, and fecal microbiota transplants, are being considered as alternative and adjunct therapies. Meta-analyses note that probiotics could offer benefits in HE treatment, but have not shown superiority over lactulose. Emerging literature suggests that fecal microbiota transplants could offer a novel strategy to treat gut dysbiosis and favorably impact HE. Finally, liver support devices and liver transplantation could offer a last-resort treatment option for persistent HE.

Besides on the reproductive performance, the light also has an important effect on the growth in birds. In the present study, we for the first time investigated effects of colored light-emitting diodes (LED) on both growth performance and fecal microbiota in meat geese. We randomly selected a total of 120 geese at birth (0-day), divided them into 3 groups evenly (i.e., 40 geese each group), and then reared them under 3 colored light-emitting diodes (i.e., blue, red, and white) with the same photoperiod for 9 wk, respectively. We collected fecal samples at the experimental day 35 and 63, respectively. We observed that geese in blue light had higher body weight than those in red and white lights at the early stage of the experiment but showed lower body weight at the late stage, particularly at day 63 (P

The microbiota that resides in the digestive tract plays pivotal role in maintaining intestinal environmental stability by promoting nutrition digestion and intestinal mucosal immunity. However, whether the intestinal microbiota in laying hens affects egg laying- performance is not known. In this study, 16S rDNA gene sequencing and fecal microbiota transplantation were used to determine the structure of the intestinal microbiota and the effect of the intestinal microbiota on egg production. The results revealed that Firmicutes were dominant in both the H (high egg laying rates) and L (low egg laying rates) groups, while Bacteroides, Actinobacteria and Proteobacteria were significantly enriched in the L group compared to the H group. The laying rates were weakly affected in H hens transplanted with the fecal microbiota from L hens, except for temporary fluctuation, while the egg laying rates were significantly increased in L hens transplanted with the fecal microbiota from H hens. Therefore, we concluded that the population structure of the intestinal microbiota varied between the H and L groups, and the intestinal microbiota of high-yield laying hens had significant effects on low-yield laying hens performance.

Fecal microbiota transplantation (FMT), the core therapy for remodeling the gut microbiota with a long medical history, has gained great attention worldwide in recent years. Increasing studies have explored its indications, methodology, efficacy, safety, and ethics. Purified forms of FMT, using an automated method for the purification of fecal microbiota from stool, has become a reality. Colonic transendoscopic enteral tubing makes frequent FMT delivery into the whole colon feasible. This review focuses on the recent progress in laboratory preparation, updated clinical strategies, novel delivery methods, and ethical issues surrounding FMT in clinical studies.

Gut microbiome composition correlates with responsiveness to immune checkpoint inhibitor therapy. In a recent study in Science, Baruch et al. manipulated gut microbiome composition in patients with refractory metastatic melanoma using fecal microbiota transplants. Fecal microbiota transplant was safe and partially effective in inducing remission in refractory patients.

Fecal microbiota for transplantation (FMT) is being studied as a potential intervention for numerous conditions. The regulation of FMT by the FDA is discussed along with FMT donor screening and manufacturing considerations. The FDA is committed to ensuring that FMT products can be safely tested in clinical trials.

Previous studies have shown that the composition and function of gut microbiota possibly contribute to the oxidative stress and host metabolism of sows. However, a functional link between gut bacteria with oxidative stress and stillbirth rate of sows remain unclear. To address this issue, the reproductive performance, oxidative stress and gut microbiota of sows with high (H) and low (L) stillbirth rate were analyzed. Results showed that, compared with the H group, the L group had a shorter farrowing duration as well as higher concentration of serum total antioxidant capacity and hydroxyl radical scavenging capacity. For the gut microbiota composition of the tested sows, 6 genera differed between the two groups, 7 genera were correlative with stillbirth rate, and 2 genera were correlated with farrowing duration. The relative abundance of Lachnospiraceae_UCG-001, Marvinbryantia and Ruminococcaceae_UCG-004 were negatively correlated with antioxidant capacity, but positively correlated with the stillbirth rate of sows. Furthermore, the microbiota functions in the polyketide sugar unit biosynthesis and nitrotoluene degradation were found to be different between the two groups through the phylotypic investigation of communities by reconstruction of unobserved states. Collectively, gut microbiota and their functions vary between sows with high or low stillbirth rate, while stillbirth rate and farrowing duration are significantly correlated with the gut microbiota composition and oxidative stress status of sows.

Alterations in the interactions between the gut microbiome, its metabolites, and the brain have been implicated in numerous brain disorders, including developmental disorders, disorders of mood and affect, neurodegenerative disorders, autoimmune conditions, eating disorders and functional gastrointestinal disorders. The specific components of brain gut microbiome disorders include disturbances of the microbial community and metabolite production, altered bidirectional signaling from the gut microbes to the brain and associated alterations in brain structure and function. These disruptions are correlated with the severity of clinical symptoms and disease progression in human and mouse models. Novel therapies are being directed at targets within the brain gut microbiome axis and include prebiotics, probiotics and postbiotics, antibiotics, and fecal microbiota transplants.

This study was conducted to evaluate the effect of dietary standardized ileal digestible lysine (SID Lys) and copper (Cu) density on growth performance, nutrient digestibility, blood profiles, fecal microbiota, backfat thickness and lean meat percentage in growing pigs. A total of 240 castrated male growing pigs [(Yorkshire × Landrace) × Duroc)] with an average BW of 22.7 ± 0.11 kg were used in this 42-day trial. Pigs were randomly allocated to 3 treatments plus control based on the BW. Basal diet contained 100% SID Lys of the estimated NRC (2012) requirement and 17 mg/kg Cu. Dietary treatments included different SID Lys of the estimated NRC (2012) requirement (100, 103 and 106%) with an extra 150 mg/kg supplemental Cu. Final BW, ADG and estimated SID Lys intake in pigs fed diets with 103 and 106% SID Lys and supplemental Cu were increased (P

The bewildering complexity of the enteric nervous system makes it susceptible to develop a wide array of motility disorders, collectively called enteric neuropathies. These gastrointestinal conditions are among the most challenging to manage, mainly given poor characterization of their etiopathophysiology and outcomes. Not surprisingly, therefore, targeted or curative therapies for enteric neuropathies are lacking and management is largely symptomatic. Nonetheless, recent advances in neurogastroenterology have witnessed improvements in established strategies, such as intestinal transplantation and the emergence of new treatments including novel drugs, electrical pacing, and manipulation of fecal microbiota, as well as stem cell and gene therapy.

Background The gut microbiota is a putative target for dietary interventions for cardio-metabolic health (CMH), including prevention of obesity, type 2 diabetes, and cardiovascular disease. This has generated considerable interest, but the actual feasibility for diet or specific foods to induce measurable, sustained and meaningful benefits for CMH risk by this route remains uncertain. Scope and approach This report summarises an expert workshop assessing the gut microbiota as a relevant, feasible and competitive target for CMH benefits by dietary interventions. It summarises the expert presentations and overall view of participants on the current status and outlook, considering also implications for the food industry. Key findings and conclusions Changing the gut microbiota by diet is possible, but an assessment of the impact on CMH risk is still needed, including clarifying advantages above other known dietary routes. The individual gut microbiota composition may in part determine the impact of diet and its effects on health. Therefore, future developments may identify individuals at risk and thus possible modification of the microbiota to achieve benefits in susceptible (sub) populations depending on their initial microbiota composition. Prebiotics currently appear to be the most promising ingredients; however, required doses may be relatively high and the actual role of gut microbiota needs further assessment. Overall, causal evidence linking gut microbiota interventions with CMH benefits are developing in preclinical models but are still lacking in humans. A significant research effort is needed and ongoing to determine whether potential effects can be reliably substantiated.

Altered intestinal microbiota composition in later life is associated with inflammaging and increased susceptibility to age–associated chronic diseases affecting various organs. Here we tested the hypothesis that manipulating the intestinal microbiota influences the development of comorbidities associated with aging, in particular, inflammation affecting intestinal epithelial barrier integrity, the retina, and the brain. Using heterochronic microbiota transplantation to exchange the intestinal microbiota of young (3 month), old (18 month), and aged (24 month) mice, we show that age–associated increases in intestinal barrier permeability, central nervous system (CNS) inflammation, and loss a of key functional retinal protein, are reversed by transfer of young donor microbiota to aged mice, but are accelerated upon transfer of aged donor microbiota into young mice. These findings demonstrate that the aged microbiota composition mediates detrimental changes in the gut–CNS axis, and suggest that microbial modulation may be of therapeutic benefit in later life.

The aim of this study was to evaluate the effect dietary supplementation of live yeast Saccharomyces cervisiae NCYC 996 (SC) on digestibility, fecal microbiota and volatile fatty acids (VFA) and serum endotoxin levels in non-exercising and exercising horses. Ten Arabian geldings were used in a 2 × 2 factorial design [10 horses, 2 treatments (with and without SC) and 2 periods (with and without exercise). The SC culture (7.5 g/meal; 1.5 × 1010 cfu/g) was given as a top-dressing. There was no effect of yeast supplementation on digestibility. Fecal yeast and bacterial counts, VFA and serum endotoxin levels were unaffected by yeast supplementation and exercise.

Abstrast The objective of this study was to evaluate the effects of wheat bran (WB) levels on the apparent total tract digestibility (ATTD) of dietary nutrient in growing pigs, and to test the hypothesis that dietary fiber could alter microbiota community and increase the synthesis of short-chain fatty acid (SCFAs), thus improving the growth performance of nursery pigs. In Exp. 1, 30 barrows with initial body weight (BW) of 40.5 ± 3.0 kg were allotted to 5 treatments in a completely randomized design. The five treatment diets included 1 control diet and 4 test diets with the WB inclusion level of 5, 15, 25 and 35%, respectively. The concentration of DE and ATTD of nutrients in diets decreased linearly (P

Clostridium difficile infection (CDI) is a common nosocomial infection that all medical practitioners must be familiar with, as all patients are at risk of developing this infectious disease. Although it has long been appreciated that this infectious disease arises secondary to the development of a colonic dysbiosis, as our understanding of the microbiome has grown substantially broader, the utilization of fecal microbiota therapy for this disease has also become a widespread reality. In addition to understanding the role of the microbiome in CDI, the poor prognosis of patients with severe, complicated CDI must also be recognized by critical care providers and abdominal surgeons. Strategies to lower the threshold for surgical consultation, and guidelines to help decide when surgery is indicated, can decrease mortality for patients. This chapter reviews these issues, as well as other aspects relevant to the treatment and care of patients with CDI.

Dietary flaxseed (FS) and its components including FS oil (FSO), secoisolariciresinol diglucoside (SDG) and fiber, are processed by the gut microbiota. These data are in support of the article entitled “Discriminatory and cooperative effects within the mouse gut microbiota in response to flaxseed and its oil and lignan components”, Journal of Nutritional Biochemistry [1]. Here we describe data generated by 16S rRNA sequencing of DNA obtained from cecum contents and feces of C57BL/6 female mice fed either a basal diet (BD, AIN93G), or isocaloric diets containing 10% FS, or 10% FS-equivalent amounts of FSO or SDG for 21 days. These include bacterial community composition and inferred KEGG pathways; the raw data are publicly available at the NCBI SRA database (BioProject ID PRJNA683934). Furthermore, this work includes detailed experimentation procedures, total bacterial counts (qPCR) in the cecum content and feces, and correlation analysis between a selected bacterial genus, Bacteroides and a predicted metabolic pathway. FS is utilized worldwide, especially for the prevention and/or treatment of diseases including cardiovascular diseases, diabetes and cancer. These data will be valuable as a reference to study different FS cultivars and SDG- or FSO- enriched products on the gut microbiota, to study gut microbial responses to FS and its components in different mouse strains and mammalian hosts to elucidate individualized effects, and to understand the importance of the gut microbiota for FS benefits.

This experiment was conducted to investigate the effects of supplementation of probiotics and prebiotics on growth performance, nutrient digestibility, relative organ weight, fecal microbiota, blood profile, and excreta noxious gas emissions in broilers. A total of 714 one-day-old mixed sex ROSS 308 broilers with the initial BW = 40 ± 0.69 g was used in a 4-week trial. All birds were raised in wire cages. Birds were randomly allotted to 7 treatments with 6 replicates per treatment and 17 broilers per pen. Dietary treatments included: 1) T1 (control), 2) T2 [T1 + 0.2% probiotics (Bacillus sp. 1 × 109 CFU, Lactobacillus sp. 1 × 108 CFU, Aspergillus niger. 1 × 107 CFU)], 3) T3 (T1 + 1% chicory fiber), 4) T4 (T1 + 1% rice bran), 5) T5 (T1+ 0.2% probiotics + 1% chicory fiber), 6) T6 (T1 + 0.2% probiotics + 1% rice bran), and 7) T7 (T1 + 0.2% probiotics + 1% chicory fiber + 1% rice bran). During d 1 to 14, broilers fed the T5, T6, and T7 diets had greater body weight gain (BWG) compared with the T1 diet (P

Current studies simply focus on the toxicity of nano-plastics, while the correlation between their toxicity and bio-distribution, as well as intestinal microorganisms is still blank. Therefore, we systematically evaluated the toxicity based on the accumulation characteristics of nano-plastics in C. elegans. Meanwhile, for the first time, human fecal microbiota was transplanted into the gut of C. elegans and found that nano-plastics can through the intestinal barrier to the whole body after oral intake and can't be drastically excreted until die, thus causing toxic effects; while human fecal microbiota transplantation can significantly improve the living state via activating PMK-1/SKN-1 pathway to promote the production of intracellular glutathione, and exogenous glutathione addition can also markedly protect nematodes against nano-plastics induced toxicity. Our results not only provide a fully understand between the accumulation characteristic and health risk of nano-plastics, but also take C. elegans and intestinal flora into the field of toxicity evolution of nanomaterials.

OBJECTIVES: The human gastrointestinal microbiota contributes to the relationship between diet and health via microbial metabolism of undigested food components. Thus, it is valuable to understand the relations between gut microorganisms and diet quality. Herein, we examined the associations between the Healthy Eating Index (HEI)-2015 and the fecal microbiota in a subset of healthy adults in the American Gut Project (AGP) cohort. METHODS: This was a cross-sectional study of healthy adults (n = 1162 (759 females); BMI: 18.5–29.9 kg/m(2); 18–65 years of age) from the AGP cohort who provided a stool sample and a time-matched Food Frequency Questionnaire (FFQ; VioScreen). Fecal samples were processed by the AGP lab. Briefly, DNA was extracted from the stool samples, and the V4 region of the 16S rRNA gene was amplified and sequenced. HEI-2015 scores were calculated using VioScreen's report of HEI-2010 scores and nutrient component percentages. The cohort was divided into tertiles based on Total Score, and components Whole Grains, Dairy, Fatty Acids, Sodium, and Saturated Fats. Differential abundance analysis was conducted using ANCOM-BC, comparing the high (T3) tertile to the low (T1) tertile for all categories. Comparisons that were statistically significant following FDR corrections are reported (q

Iron is an essential trace mineral for the growth, systemic metabolism, and immune response. Dysregulation of iron homeostasis is linked with the development and progression of various diseases. The excessive iron accumulation is highly associated with inflammatory diseases and cancer while iron deficiency leads to growth retardation. Multiple studies have suggested that iron dysbiosis results in alteration of gut microbiota, leading to the disruption of microbial diversity, increase of pathogen abundance and induction of intestinal inflammation. However, screening the widespread studies in the past decades, the association between iron availability and gut microbiota are not completely explored. Furthermore, non-invasive and convenient approach to determine the tissue iron is still limited. In the current study, a murine model for iron dysbiosis was established. 16S rRNA amplicon sequencing and innovated bioinformatic algorithms are utilized to identify key microbiota. Leveraging on these key microbiotas, we established an easily assessible prediction model, which could accurately distinguish the individual under either iron-deprived or iron-fortified condition and precisely predict the tissue iron level of intestine epithelial cells and liver. This could be further applied for early diagnosis of iron dysbiosis-related diseases as a non-invasive approach. Funding Statement: This work was support by ‘GDAS’ Project of Science and Technology Development (Grant No. 2018GDASCX-0806) to Liwei Xie and supported by National Natural Science Foundation of China (Grant No.: 8187050617) to Jiyang Pan. Declaration of Interests: The authors declare that there is no conflict of financial or research interest. Ethics Approval Statement: The animal protocol was proved by the Institute Animal Care Use Committees of GDIM (Permission #: GT-IACUC201704071).

The present study was conducted to evaluate the effects of dietary synbiotic supplementation on reproductive performance, plasma indexes, and fecal microbiota composition and metabolite level in pregnant and lactating sows. Forty-eight pregnant Bama mini-pigs with 3–7 parities were randomly allocated to a control group (a basal diet), an antibiotic group (50 g/t virginiamycin), or a synbiotic group (200 mL/d·head fermentation broth and 500 g/t xylo-oligosaccharides). Compared with the control group, dietary synbiotic supplementation increased the piglet survival rate and decreased colostrum somatic cell numbers, while synbiotic or antibiotic supplementation improved plasma lipid metabolism. The synbiotic supplementation increased fecal Simpson and Shannon indices, and the relative abundances of Coprococcus and Ruminococcus on day 105 of pregnancy compared with the other two groups. Spearman correlation analysis showed a positive correlation between Ruminococcus abundance and bioamine level but a negative correlation between Desulfovibrio abundance and butyrate level. These findings suggested that dietary synbiotic supplementation can improve piglet’s survival and lipid metabolism by altering gut microbiota diversity and composition in pregnant and lactating sows.

Summary Infants born by vaginal delivery are colonized with maternal fecal microbes. Cesarean section (CS) birth disturbs mother-to-neonate transmission. In this study (NCT03568734), we evaluated whether disturbed intestinal microbiota development could be restored in term CS-born infants by postnatal, orally delivered fecal microbiota transplantation (FMT). We recruited 17 mothers, of whom seven were selected after careful screening. Their infants received a diluted fecal sample from their own mothers, taken 3 weeks prior to delivery. All seven infants had an uneventful clinical course during the 3-month follow-up and showed no adverse effects. The temporal development of the fecal microbiota composition of FMT-treated CS-born infants no longer resembled that of untreated CS-born infants but showed significant similarity to that of vaginally born infants. This proof-of-concept study demonstrates that the intestinal microbiota of CS-born infants can be restored postnatally by maternal FMT. However, this should only be done after careful clinical and microbiological screening.

Different culture-dependent and independent methods were applied to investigate the population of bifidobacteria and lactobacilli in the feces of five healthy subjects. Bacteria were isolated on MRS, a complex medium supporting growth of lactobacilli and bifidobacteria, and on three selective media for bifidobacteria and two for lactobacilli. Taxonomic characterization of the isolates was carried out by RAPD-PCR and partial 16S sequencing. The selectivity of genus-specific media was also investigated by challenging colonies from MRS plates to grow onto each medium. In parallel, a quantitative and qualitative description of bifidobacteria and lactic acid bacteria was obtained by FISH, qPCR, TRFLP, and 16S rRNA gene sequencing. Bifidobacteria did not fail to grow on their specific media and were easily isolated and enumerated, showing comparable quantitative data among culture-dependent and-independent techniques. The Bifidobacterium species identified on plates and those extracted from TRFLP and 16S rRNA gene sequencing were mostly overlapping. Selective media for lactobacilli gave unsuitable results, being too stringent or too permissive. The quantification of lactobacilli through selective plates, qPCR, FISH, and 16S rRNA gene sequencing gave unreliable results. Therefore, unlike bifidobacteria, intestinal lactobacilli are still problematic in terms of quantification and accurate profiling at level of species and possibly of strains by both culture-dependent and culture-independent techniques. (C) 2015 Elsevier Ltd. All rights reserved.

This study investigated the effects of Ganoderma lucidum extract on the growth performance, fecal microbiome, and bursal transcriptome of broilers. A total of 60 one-day-old Ross 308 male broiler chicks were randomly assigned into 2 dietary treatments with 5 replicate cages per treatment and 6 birds per cage. The dietary treatments consisted of a basal diet as control and a diet of control plus 1 g/L G. lucidum extract in drinking water. G. lucidum extract was supplied on days 14 through 16, 21 through 23, and 28 through 30. No significant difference was observed in growth performance in broilers after feeding with G. lucidum extract. G. lucidum extract treatment improved (P

Cellobiose is a disaccharide with potential prebiotic effects, as demonstrated in different animal species, but not yet in horses. It was, therefore, the aim of the present study to evaluate the impact of dietary cellobiose on the fecal microbiota of horses. Eight healthy adult horses and two ponies were included in this study. The animals received a diet without or with 10 g and 20 g cellobiose per day for 14 days each. At the end of the feeding periods, fresh fecal samples were collected to measure bacterial metabolites and the microbial composition. For the microbiota analysis, 16S rRNA gene sequencing was used. Cellobiose was well accepted and tolerated by the animals. The lowest fecal concentrations of D-lactate, propionic acid, i-valeric acid, and total short-chain fatty acids were measured at the dose 10 g cellobiose per horse per day (quadratic effect: P.05). A dose-dependent increase of the relative abundance of Firmicutes (P = .049), Coriobacteriales (P.001), and Clostridium (P = .031) could be detected. In addition, a dose-dependent decrease of the relative abundance of Bacteroidetes (P = .035) was observed. In conclusion, the increase of Coriobacteriales and Clostridium indicates a bacterial fermentation of cellobiose in the equine intestine, as members of both groups exert saccharolytic activity. As clostridia have previously been assumed to be a key component of the intestinal microbiota in horses, the observed increase of Clostridium in the feces might indicate beneficial and potentially prebiotic effects of cellobiose in horses. However, this finding requires further investigation, particularly with regard to the Clostridium species that have been promoted by dietary cellobiose.

OBJECTIVES: Prebiotics are defined as substrates that are selectively utilized by host microorganisms conferring a health benefit. We aimed to determine the effects of the prebiotics fructooligosaccharides (FOS) and galactooligosaccharides (GOS) on the fecal microbiota and gastrointestinal health in adults. METHODS: We conducted a randomized, double-blind, placebo-controlled, crossover trial in healthy adults (n = 26) 25–45 years of age. Participants consumed two 4-week treatments in a randomized, counterbalanced order. The prebiotic beverage (PRE) was 8 oz low-fat lactose-free milk with 5 g FOS and 5 g GOS. The control beverage (CON) was 8 oz low-fat lactose-free milk without the added prebiotics. Each condition was separated by a 4-week washout. Fecal samples were collected at baseline and end of each condition. Fecal short-chain fatty acid (SCFA) concentrations were quantified using gas chromatography-mass spectrometry (GC-MS). Fecal pH was measured using a pH meter. Gastrointestinal health was assessed using the Bristol stool scale and a stool frequency and ease of passage log before the first and during the last week of each condition. SAS 9.4 was used to conduct general linear mixed modeling with treatment as a fixed effect and participant and period as random effects. Normality was assessed using the Shapiro-Wilk test and log and arcsine transformations were applied as needed. RESULTS: There was a 153% increase in fecal bifidobacteria relative abundances in the prebiotic group compared to control (CON: 2.8 ± 0.6, PRE: 6.9 ± 1.7; P = 0.002). No differences were detected between the groups in fecal acetate (CON: 278 ± 30.1, PRE: 231 ± 24.4; P = 0.2), butyrate (CON: 68.4 ± 10.1, PRE: 62.9 ± 12.2; P = 0.4), or propionate (CON: 76.5 ± 7.5, PRE: 76.7 ± 12.5; P = 0.4) concentrations, or fecal pH (CON: 6.86 ± 0.10, PRE: 6.91 ± 0.14; P = 0.5). Stool frequency (stool/day) increased by 26% in PRE compared to CON (CON: 1.0 ± 0.1, PRE: 1.3 ± 0.1; P = 0.01). Ease of stool passage tended to improve in PRE compared to CON (CON: 2.2 ± 0.1, PRE: 2.0 ± 0.1; P = 0.1). There was no difference in stool consistency (CON: 3.7 ± 0.3, PRE: 3.7 ± 0.2; P = 0.8). CONCLUSIONS: These findings are suggestive of the beneficial health effects of consumption of the prebiotics FOS and GOS on gastrointestinal health in adults. FUNDING SOURCES: USDA National Institute of Food and Agriculture, Hatch Project 1009249.

Background PD-1 inhibition (α-PD-1) can lead to deep, durable responses in mCRPC, but only in a minority of patients (pts). We previously reported 5 (18%) responders among 28 pts. No marker has been shown to universally predict response. Analysis of fecal microbiota from pts with epithelial cancers showed an association between elevated Akkermansia muciniphila (A. muc) levels and response to α-PD-1. To evaluate predictive markers, we treated an additional 30 pts obtaining tumor biopsies, blood, and fecal specimens collected for analysis. Methods 30 pts with mCRPC progressing on Enz received α-PD-1 pembrolizumab 200 mg IV every 3 weeks for 4 doses with continued Enz. Prior chemotherapy for mCRPC was prohibited. The primary endpoint was the proportion of pts with a prostate-specific antigen (PSA) decline ≥ 50%. The secondary endpoints were objective response, PSA progression-free survival (PFS), radiographic PFS, overall survival (OS) and correlative studies. Results Four of 30 (13%) achieved a PSA reduction ≥ 50%. Six of 24 (25%) pts with measurable disease responded radiographically. After median follow up of 17.4 months (mos), median PSA PFS was 5.57 mos (95%CI: 3.48-8.06). Median OS was 17.25 mos (95% CI: 7.71-17.68). Of 27 pts evaluable for radiographic PFS, 17 (63%) have progressed; median radiographic PFS was 5.26 mos (95% CI: 2.6-11.2). Eight pts had immune related adverse events. Single cell analysis revealed that immune cells represent an average 0.5% of cells in tumor biopsies. Single cell transcriptomic analysis prior to α-PD-1 in 12 pts revealed enrichment in a CD8+ exhausted T cell population (p Conclusions Using single cell RNA sequencing, we reveal a T-cell signature associated with response, an observation not possible at the bulk transcriptome level. Responders had lower levels of fecal A. muc than non-responders, suggesting markers of α-PD-1 response in mCRPC may be different than in other cancer types. Clinical trial identification NCT02312557. Legal entity responsible for the study Julie N Graff. Funding Merck Sharp & Dohme. Disclosure J.N. Graff: Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: Merck Sharp & Dohme; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: Janssen; Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: Sanofi; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: Bayer; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): Astellas/Pfizer. A.E. Moran: Research grant / Funding (institution): Merck Sharp & Dohme. J.J. Alumkal: Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): Astellas Pharma; Honoraria (self), Advisory / Consultancy: Bayer; Honoraria (self), Advisory / Consultancy: Janssen Biotech; Research grant / Funding (institution): Aragon Pharmaceuticals; Research grant / Funding (institution): Novartis; Research grant / Funding (institution): Zenith Epigenetics Ltd; Research grant / Funding (institution): Gilead Sciences Inc. R.C. Bergan: Leadership role, Licensing / Royalties, Full / Part-time employment: Third Coast Therapeutics. T.M. Beer: Research grant / Funding (institution): Alliance Foundation Trials; Advisory / Consultancy, Research grant / Funding (institution): Boehringer Ingelheim; Research grant / Funding (institution): Corcept Therapeutics; Research grant / Funding (institution): Endocyte Inc; Research grant / Funding (institution): Janssen Research & Development; Research grant / Funding (institution): Medivation; Research grant / Funding (institution): OncoGenex; Research grant / Funding (institution): Sotio; Research grant / Funding (institution): Theraclone Sciences/OncoResponse; Advisory / Consultancy: AbbVie; Honoraria (self), Advisory / Consultancy: AstraZeneca; Honoraria (self), Advisory / Consultancy: Astellas Pharma; Honoraria (self), Advisory / Consultancy: Bayer; Honoraria (self), Advisory / Consultancy: Clovis Oncology; Honoraria (self), Advisory / Consultancy: GlaxoSmithKline; Honoraria (self), Advisory / Consultancy: Janssen Biotech; Honoraria (self), Advisory / Consultancy: Janssen Japan; Honoraria (self), Advisory / Consultancy: Merck; Honoraria (self), Advisory / Consultancy: Pfizer. All other authors have declared no conflicts of interest.

Fecal microbiota transplantation has emerged as an increasingly common treatment for patients with refractory Clostridium difficile infection. Although it can be relatively simple to perform, a number of challenges need to be overcome before this procedure is widely accepted in mainstream clinical practice. Most of the solutions to these challenges already exist, but some need further optimization and testing. Standardized fecal microbiota is being developed as a therapeutic agent, although it clearly challenges some of the existing paradigms of drug development, delivery, and regulation.