Clostridium Cluster XIVa Research Articles

Prebiotic effects of commercial apple juice in high-fat diet fed rat

ObjectivesApples are one of the most frequently consumed fruits and are effective in preventing lifestyle-related and other diseases. However, few studies have been conducted to evaluate health benefits of processed apple products such as juice. In this study, we analyzed the health benefits of consuming apple juice, focusing on changes in the gut microbiota, which plays an important role in maintaining human health.ResultsRats were fed apple juice ad libitum, and the relative abundances of various gut microbiota in fecal samples were analyzed. In addition, rats treated apple juice were fed with a high-fat diet, and body weight, plasma triglyceride, glucose, and cholesterol levels were measured. The relative abundance of Clostridium cluster XIV did not change with the treatment of apple juice, but the relative abundance of Clostridium cluster IV was significantly decreased. In contrast, the relative abundances of Lactobacillus and Bifidobacterium, which provide benefits to the human body, were significantly increased by 3-fold and 10-fold, respectively, with apple juice consumption. When apple juice-treated rats were fed a high-fat diet, the increase in body weight, liver fat, and blood lipid parameters were all suppressed compared to high-fat alone group.ConculusionThis study suggests that the consumption of apple juice changes the gut microbiota, exerts a prebiotic effect, and is effective in improving lifestyle-related diseases.

The Gut Microbiome in Aging and Ovarian Cancer.

The gut microbiome changes with age and affects regions beyond the gut, including the ovarian cancer tumor microenvironment. In this review summarizing the literature on the gut microbiome in ovarian cancer and in aging, we note trends in the microbiota composition common to both phenomena and trends that are distinctly opposite. Both ovarian cancer and aging are characterized by an increase in proinflammatory bacterial species, particularly those belonging to phylum Proteobacteria and genus Escherichia, and a decrease in short chain fatty acid producers, particularly those in Clostridium cluster XIVa (family Lachnospiraceae) and the Actinobacteria genus Bifidobacterium. However, while beneficial bacteria from family Porphyromonadaceae and genus Akkermansia tend to increase with normal, healthy aging, these bacteria tend to decrease in ovarian cancer, similar to what is observed in obesity or unhealthy aging. We also note a lack in the current literature of research demonstrating causal relationships between the gut microbiome and ovarian cancer outcomes and research on the gut microbiome in ovarian cancer in the context of aging, both of which could lead to improvements to ovarian cancer diagnosis and treatment.

Progression of swine fecal microbiota during early stages of life and its association with performance: a longitudinal study

BackgroundIt is vital to understand healthy gut microbiota composition throughout early life stages when environments are changing, and immunity is developing. There are limited large-scale longitudinal studies classifying healthy succession of swine microbiota. The objectives of this study were to (a) determine the microbiota composition of fecal samples collected from piglets within a few days after birth until one-week post-weaning, and (b) investigate the associations of early fecal microbiota with pig growth performance in nursery and later growing stages. Fecal samples were collected from nine cohorts of 40 pigs (n = 360) from distinct farrowing sources in Ontario and Quebec, Canada at four timepoints from birth to one-week post-weaning, with pig body weight was recorded at each fecal sampling.ResultsMicrobiota was dominated by the phyla Firmicutes, Bacteroides and Proteobacteria. There were notable differences in genera abundance between pigs from different provinces and farming systems. Over the early life stage, the genera Bacteroides, Escherichia/Shigella, and Clostridium cluster XIVa were abundant preweaning, while Prevotella dominated post-weaning. Hierarchical clustering identified three major stages of microbiota development, each associated with distinct composition. Stage one occurs from birth to 7 days, stage two from 7 days after birth until weaning, and stage three from weaning to one-week post-weaning. Three enterotypes were identified in stage two that showed differences in growth before weaning, and in the grower production stage. Piglets with a microbiota enterotype characterized by higher abundance of Prevotella and unclassified Ruminococcaceae had lower growth performance in the pre-weaning stage, and the growing stage.ConclusionThese findings help identify the timing of microbiota shifts across early swine life which may be the optimal time for external intervention to shift the microbiota to a beneficial state. The project findings should help decrease antimicrobial use, increase animal welfare, and have positive economic impacts.

Dietary Resistant Starch Regulates Bile Acid Metabolism by Modulating the FXR/LRH-1 Signaling Pathway in Broilers

This study aimed to investigate the effects of dietary corn-resistant starch on the bile acid metabolism of broilers. In total, 80, 1-day-old male broilers were randomly distributed into two groups fed either the basic normal corn–soybean diet or a diet supplemented with 40 g/kg of corn-resistant starch. The results showed that dietary supplementation of 4% corn-resistant starch increased the F/G during the periods from 21 to 42 d. Resistant starch supplementation reduced the lipid levels in plasma, and the contents of total bile acids were increased with the altered bile acid profile in the ileum. A diet with corn resistant starch decreased the enzyme contents of the classical pathway of bile acid synthesis and activated the signaling pathway of FXR/LRH-1 in the liver. A decreased abundance of Clostridium cluster XIVa was found in the ileal digesta of the resistant starch group, and its abundance was negatively correlated with the level of lithocholic acid. In summary, the RS was effective at reducing broiler plasma and liver lipid levels, which was probably due to the change in bile acid synthesis and reabsorption capacities. These findings provided a unique landscape of the relationship between bile acid metabolism and resistant starch in broilers.

Description of Fusibacillus kribbianus gen. nov., sp. nov., a fusiform anaerobe isolated from pig feces

ObjectiveThe family Lachnospiraceae is affiliated with the order Clostridiales and was originally contained within Clostridial cluster XIVa. The members of Lachnospiraceae inhabiting the gut comprise the chemoorganotrophic genera, generating sundry short-chain fatty acids to supply energy to the host, and are considered to be related to obesity and gut health. MethodsThe polyphasic taxonomic approach was used to characterize the isolate YH-rum2234T. A detailed metabolic analysis was conducted to compare the novel isolate with related strains within the family Lachnospiraceae. ResultsA fusiform, obligately anaerobic, Gram-stain-negative bacterium, YH-rum2234T, was isolated from pig feces. Analysis of the 16S rRNA gene sequence revealed that the similarities between the isolate and the familiarly interrelated strain Lientehia hominis KCTC 25345T was 94.3%. The average nucleotide identities and genome-to-genome distances of YH-rum2234T and its closely related strains were below 85.5% and 32.5%, respectively. The G + C content of the genomic DNA was 49.2 mol%. The main fatty acids were C16:0, C14:0, and C14:0 DMA. The major polar lipids were aminophospholipids. The cell wall did not contain the peptidoglycan meso-diaminopimelic acid. ConclusionGiven the chemotaxonomic, phenotypic, and phylogenetic properties, YH-rum2234T (=KCTC 25710T = DSMZ 116041T) represents a new genus and species in the family Lachnospiraceae. Fusibacillus kribbianus gen. nov., sp. nov. is the proposed name.

The Effect of Supplementation with Betaine and Zinc on In Vitro Large Intestinal Fermentation in Iberian Pigs under Heat Stress

We investigated the effects of betaine and zinc on the in vitro fermentation of pigs under heat stress (HS). Twenty-four Iberian pigs (43.4 ± 1.2 kg) under HS (30 °C) were assigned to treatments for 4 weeks: control (unsupplemented), betaine (5 g/kg), and zinc (0.120 g/kg) supplemented diet. Rectal content was used as the inoculum in 24-hincubations with pure substrates (starch, pectin, inulin, cellulose). Total gas, short-chain fatty acid (SCFA), and methane production and ammonia concentration were measured. The abundance of total bacteria and several bacterial groups was assessed. Betaine increased the acetate production with pectin and inulin, butyrate production with starch and inulin, and ammonia concentration, and decreased propionate production with pectin and inulin. The abundance of Bifidobacterium and two groups of Clostridium decreased with betaine supplementation. Zinc decreased the production of SCFA and gas with starch and inulin, associated with diminished bacterial activity. Propionate production decreased with starch, pectin, and inulin while butyrate production increased with inulin, and isoacid production increased with cellulose and inulin in pigs supplemented with zinc. The ammonia concentration increased for all substrates. The Clostridium cluster XIV abundance decreased in pigs fed zinc supplemented diets. The results reported were dependent on the substrate fermented, but the augmented butyrate production with both betaine and zinc could be of benefit for the host.

Efficient butyrate production from rice straw in an optimized cathodic electro-fermentation process

Butyrate production from renewable biomass shows great potential against climate change and over-consumption of fossil fuels. Herein, key operational parameters of a cathodic electro-fermentation (CEF) process were optimized for efficient butyrate production from rice straw by mixed culture. The cathode potential, controlled pH and initial substrate dosage were optimized at −1.0 V (vs Ag/AgCl), 7.0 and 30 g/L, respectively. Under the optimal conditions, 12.50 g/L butyrate with yield of 0.51 g/g-rice straw were obtained in batch-operated CEF system. In fed-batch mode, butyrate production significantly increased to 19.66 g/L with the yield of 0.33 g/g-rice straw, but 45.99% butyrate selectivity still needs to be improved in future. Enriched butyrate producing bacteria (Clostridium cluster XIVa and IV) with proportion of 58.75% on the 21st day of the fed-batch fermentation, contributed to the high-level butyrate production. The study provides a promising approach for efficient butyrate production from lignocellulosic biomass.

Effects of bis-chelated copper in growth performance and gut health in broiler chickens subject to coccidiosis vaccination or coccidia challenge.

Copper (Cu) is widely used at high levels as growth promoter in poultry, the alternative source of Cu to replace the high level of inorganic Cu at poultry farm remains to be determined. Three floor pen experiments were conducted to evaluate the effects of Cu methionine hydroxy-analogue chelate (Cu-MHAC, MINTREX®Cu, Novus International, Inc.) on growth performance and gut health in broilers in comparison to CuSO4 and/or tribasic copper chloride (TBCC). There were 3 treatments in experiment#1 (0, 30 and 75ppm Cu-MHAC) and experiment#2 (15 and 30ppm Cu-MHAC, and 125 ppm CuSO4), and 4 treatments in experiment #3 (15 and 30ppm Cu-MHAC, 125ppm CuSO4 and 125ppm TBCC) with nine replicates pens of 10-13 birds in each treatment. The levels of other minerals were equal among all treatments within each experiment. All birds were orally gavaged with a coccidiosis vaccine at 1x recommended dose on d0 in experiment#1 and #2 and 10x recommended dose on d15 in experiment #3. Data were analyzed by one-way ANOVA, means were separated by Fisher's protected LSD test. A p ≤ 0.05 was considered statistically different. In experiment #1, 30 and 75ppm Cu-MHAC improved FCR during grower phase, increased jejunal villus height and reduced jejunal crypt depth, 30 ppm Cu-MHAC increased cecal Lactobacillus spp. abundance in 41days broilers. In experiment #2, compared to CuSO4, 15ppm Cu-MHAC increased cumulative performance index in 28days broilers, 15 and/or 30ppm Cu-MHAC improved gut morphometry, and 30ppm Cu-MHAC reduced the abundance of E. coli and Enterobacteriaceae in cecum in 43days broilers. In experiment #3, 15ppm and 30ppm Cu-MHAC improved FCR vs. CuSO4 during starter phase, reduced the percentage of E. coli of total bacteria vs. TBCC, 30ppm Cu-MHAC increased the percentages of Lactobacillus acidophilus, Lactobacillus spp. and Clostridium cluster XIVa of total bacteria vs. both CuSO4 and TBCC in the cecum of 27days broilers. In summary, low doses of Cu-MHAC had comparable growth performance to high dose of TBCC and CuSO4 while improving gut microflora and gut morphometry in broilers subject to coccidiosis vaccination or coccidia challenge, indicating that low doses of bis-chelated Cu could be used as a complimentary strategy to improve animal gut health.

Dietary-Induced Bacterial Metabolites Reduce Inflammation and Inflammation-Associated Cancer via Vitamin D Pathway.

Environmental factors, including westernised diets and alterations to the gut microbiota, are considered risk factors for inflammatory bowel diseases (IBD). The mechanisms underpinning diet-microbiota-host interactions are poorly understood in IBD. We present evidence that feeding a lard-based high-fat (HF) diet can protect mice from developing DSS-induced acute and chronic colitis and colitis-associated cancer (CAC) by significantly reducing tumour burden/incidence, immune cell infiltration, cytokine profile, and cell proliferation. We show that HF protection was associated with increased gut microbial diversity and a significant reduction in Proteobacteria and an increase in Firmicutes and Clostridium cluster XIVa abundance. Microbial functionality was modulated in terms of signalling fatty acids and bile acids (BA). Faecal secondary BAs were significantly induced to include moieties that can activate the vitamin D receptor (VDR), a nuclear receptor richly represented in the intestine and colon. Indeed, colonic VDR downstream target genes were upregulated in HF-fed mice and in combinatorial lipid-BAs-treated intestinal HT29 epithelial cells. Collectively, our data indicate that HF diet protects against colitis and CAC risk through gut microbiota and BA metabolites modulating vitamin D targeting pathways. Our data highlights the complex relationship between dietary fat-induced alterations of microbiota-host interactions in IBD/CAC pathophysiology.

Dietary and phytogenic inclusion effects on the broiler chicken cecal ecosystem

Dietary modulation in broilers is crucial for the establishment of beneficial microbiota and, subsequently, the promotion of intestinal health. In this trial, a 2 × 2 factorial design was used with two different specifications with respect to dietary metabolizable energy (ME) and crude protein (CP) levels (i.e., 95% and 100% of recommendations) and phytogenic levels (0 and 150 mg/kg). Levels of total bacteria, Bacteroides spp., Lactobacillus spp., and Clostridium cluster XIVa attached to the cecal mucosa and in the cecal digesta were lower in broilers fed the 95% ME and CP specification diets, as was the molar ratio of butyric acid. In addition, the relative activity of autoinducers-2 (AI-2) and the expression levels of TLR4 and AvBD6 were increased. Phytogenic supplementation reduced cecal digesta levels of Escherichia coli and Clostridium cluster I levels, and increased Clostridium cluster IV levels. Moreover, the butyric acid molar ratio and the relative activity of AI-2 were increased, whereas the concentration of branched VFAs and the expression of AvBD6 and LEAP2 were reduced by phytogenic administration. Dietary specifications and phytogenic interactions were shown for the cecal-attached microbiota composition, metabolic activity of digesta microbiota, relative expression of autoinducers-2, and relative expression of toll-like signaling molecules and host antimicrobial peptides. In conclusion, it has been shown that ME and CP dietary specifications, combined or not with phytogenics, modulate multilevel gut biomarkers ranging from microbiota composition and metabolic activity to microbial communications and host signaling, inflammation, and defense.

Treatment of peanut allergy and colitis in mice via the intestinal release of butyrate from polymeric micelles

The microbiome modulates host immunity and aids the maintenance of tolerance in the gut, where microbial and food-derived antigens are abundant. Yet modern dietary factors and the excessive use of antibiotics have contributed to the rising incidence of food allergies, inflammatory bowel disease and other non-communicable chronic diseases associated with the depletion of beneficial taxa, including butyrate-producing Clostridia. Here we show that intragastrically delivered neutral and negatively charged polymeric micelles releasing butyrate in different regions of the intestinal tract restore barrier-protective responses in mouse models of colitis and of peanut allergy. Treatment with the butyrate-releasing micelles increased the abundance of butyrate-producing taxa in Clostridium cluster XIVa, protected mice from an anaphylactic reaction to a peanut challenge and reduced disease severity in a T-cell-transfer model of colitis. By restoring microbial and mucosal homoeostasis, butyrate-releasing micelles may function as an antigen-agnostic approach for the treatment of allergic and inflammatory diseases.

Mining the microbiota to identify gut commensals modulating neuroinflammation in a mouse model of multiple sclerosis

BackgroundThe gut microbiome plays an important role in autoimmunity including multiple sclerosis and its mouse model called experimental autoimmune encephalomyelitis (EAE). Prior studies have demonstrated that the multiple sclerosis gut microbiota can contribute to disease, hence making it a potential therapeutic target. In addition, antibiotic treatment has been shown to ameliorate disease in the EAE mouse model of multiple sclerosis. Yet, to this date, the mechanisms mediating these antibiotic effects are not understood. Furthermore, there is no consensus on the gut-derived bacterial strains that drive neuroinflammation in multiple sclerosis.ResultsHere, we characterized the gut microbiome of untreated and vancomycin-treated EAE mice over time to identify bacteria with neuroimmunomodulatory potential. We observed alterations in the gut microbiota composition following EAE induction. We found that vancomycin treatment ameliorates EAE, and that this protective effect is mediated via the microbiota. Notably, we observed increased abundance of bacteria known to be strong inducers of regulatory T cells, including members of Clostridium clusters XIVa and XVIII in vancomycin-treated mice during the presymptomatic phase of EAE, as well as at disease peak. We identified 50 bacterial taxa that correlate with EAE severity. Interestingly, several of these taxa exist in the human gut, and some of them have been implicated in multiple sclerosis including Anaerotruncus colihominis, a butyrate producer, which had a positive correlation with disease severity. We found that Anaerotruncus colihominis ameliorates EAE, and this is associated with induction of RORγt+ regulatory T cells in the mesenteric lymph nodes.ConclusionsWe identified vancomycin as a potent modulator of the gut-brain axis by promoting the proliferation of bacterial species that induce regulatory T cells. In addition, our findings reveal 50 gut commensals as regulator of the gut-brain axis that can be used to further characterize pathogenic and beneficial host-microbiota interactions in multiple sclerosis patients. Our findings suggest that elevated Anaerotruncus colihominis in multiple sclerosis patients may represent a protective mechanism associated with recovery from the disease.9r9NT9qYv7iDsLZaQd6sb5Video

The Effects of Bacillus licheniformis-Fermented Products on the Microbiota and Clinical Presentation of Cats with Chronic Diarrhea.

Simple SummaryProbiotics are defined as live microorganisms that, when administered in adequate amounts, confer a health benefit to the host. Probiotics have also been introduced in companion animals in recent years, and the main priority of probiotic use has focused on the health of individual animals. This study aimed to compare the fecal microbiota of cats with chronic diarrhea with that of healthy cats from the same household and evaluate the effectiveness of oral administration of Bacillus licheniformis-fermented products (BLFP) in relieving clinical signs and altering the intestinal microbiota in diarrheal cats. Overall, this study provides basic information on the types and ratios of fecal microbiota in healthy cats and cats with chronic diarrhea. Our results also demonstrated that oral administration of BLFP could significantly impact the relief of clinical gastrointestinal symptoms and the gastrointestinal microbiomes in cats with diarrhea.Bacillus licheniformis-fermented products (BLFP) are probiotics with antibacterial, antiviral, and anti-inflammatory properties that can improve growth performance. This study aimed to compare the fecal microbiota of diarrheal cats with chronic diarrhea (n = 8) with that of healthy cats (n = 4) from the same household using next-generation sequencing, and evaluate the effectiveness of oral administration of BLFP in relieving clinical signs and altering the intestinal microbiota in diarrheal cats. Six out of eight diarrheal cats showed clinical improvement after BLFP administration for 7 days, and the stool condition of the other two was normal. A higher Firmicutes/Bacteroidetes ratio was noted in the feces of diarrheal cats without clinical improvement as compared with those in the healthy cats and in the diarrheal cats with clinical improvement after receiving BLFP. The phylum Bacteroidetes and class Bacteroidia decreased significantly in diarrheal cats regardless of BLFP administration. Blautia spp., Ruminococcus torques, and Ruminococcus gnavus, which belong to the Clostridium cluster XIVa and have been reported as beneficial to intestinal health, increased significantly in feces after treatment. Furthermore, Clostridium perfringens also significantly decreased in diarrheal cats after BLFP administration. Overall, BLFP could be a potential probiotic to relieve gastrointestinal symptoms and improve fecal microbiota in cats with chronic diarrhea.

Probiotic Potential of Clostridium spp.-Advantages and Doubts.

Clostridium spp. is a large genus of obligate anaerobes and is an extremely heterogeneous group of bacteria that can be classified into 19 clusters. Genetic analyses based on the next-generation sequencing of 16S rRNA genes and metagenome analyses conducted on human feces, mucosal biopsies, and luminal content have shown that the three main groups of strict extremophile anaerobes present in the intestines are Clostridium cluster IV (also known as the Clostridium leptum group), Clostridium cluster XIVa (also known as the Clostridium coccoides group) and Bacteroides. In addition to the mentioned clusters, some C. butyricum strains are also considered beneficial for human health. Moreover, this bacterium has been widely used as a probiotic in Asia (particularly in Japan, Korea, and China). The mentioned commensal Clostridia are involved in the regulation and maintenance of all intestinal functions. In the literature, the development processes of new therapies are described based on commensal Clostridia activity. In addition, some Clostridia are associated with pathogenic processes. Some C. butyricum strains detected in stool samples are involved in botulism cases and have also been implicated in severe diseases such as infant botulism and necrotizing enterocolitis in preterm neonates. The aim of this study is to review reports on the possibility of using Clostridium strains as probiotics, consider their positive impact on human health, and identify the risks associated with the expression of their pathogenic properties.

The gut microbiota composition in patients with right- and left-sided colorectal cancer and after curative colectomy, as analyzed by 16S rRNA gene amplicon sequencing

BackgroundGut pathological microbial imbalance or dysbiosis is closely associated with colorectal cancer. Although there are observable differences in molecular and clinical characteristics between patients with right- and left-sided colon cancer, differences in their gut microbiomes have not been thoroughly investigated. Furthermore, subsequent changes in microbiota status after partial colectomy remain unknown. We examined the human gut microbiota composition to determine its relationship with colon cancer and partial colon resection according to location.MethodsStool samples from forty-one subjects (10 in the control group, 10 in the right-sided colon cancer [RCC] group, 6 in the sigmoid colon cancer [SCC] group, 9 in the right colon resection [RCR] group and 6 in the sigmoid colon resection [SCR] group) were collected, and DNA was extracted. After terminal restriction fragment length polymorphism (T-RFLP) analysis, the samples were subjected to 16S rRNA gene amplicon sequencing, and the metabolic function of the microbiota was predicted using PICRUSt2.ResultsT-RFLP analysis showed a reduced ratio of clostridial cluster XIVa in the SCC patients and clostridial cluster IX in the RCC patients, although these changes were not evident in the RCR or SCR patients. 16S rRNA gene amplicon sequencing demonstrated that the diversity of the gut microbiota in the RCC group was higher than that in the control group, and the diversity in the SCR group was significantly higher than that in the RCR group. Principal coordinate analysis (PCoA) revealed significant differences according to the group. Analyses of the microbiota revealed that Firmicutes was significantly dominant in the RCC group and that the SCC group had a higher abundance of Verrucomicrobia. At the genus level, linear discriminant analysis effect size (LEfSe) revealed several bacteria, such as Ruminococcaceae, Streptococcaceae, Clostridiaceae, Gemellaceae, and Desulfovibrio, in the RCC group and several oral microbiomes in the SCC group. Metabolic function prediction revealed that cholesterol transport- and metabolism-related enzymes were specifically upregulated in the RCC group and that cobalamin metabolism-related enzymes were downregulated in the SCC group.ConclusionGut microbial properties differ between RCC and SCC patients and between right hemicolectomy and sigmoidectomy patients and may contribute to clinical manifestations.

Gut metabolites predict Clostridioides difficile recurrence

BackgroundClostridioides difficile infection (CDI) is the most common hospital acquired infection in the USA, with recurrence rates > 15%. Although primary CDI has been extensively linked to gut microbial dysbiosis, less is known about the factors that promote or mitigate recurrence. Moreover, previous studies have not shown that microbial abundances in the gut measured by 16S rRNA amplicon sequencing alone can accurately predict CDI recurrence.ResultsWe conducted a prospective, longitudinal study of 53 non-immunocompromised participants with primary CDI. Stool sample collection began pre-CDI antibiotic treatment at the time of diagnosis, and continued up to 8 weeks post-antibiotic treatment, with weekly or twice weekly collections. Samples were analyzed using (1) 16S rRNA amplicon sequencing, (2) liquid chromatography/mass-spectrometry metabolomics measuring 1387 annotated metabolites, and (3) short-chain fatty acid profiling. The amplicon sequencing data showed significantly delayed recovery of microbial diversity in recurrent participants, and depletion of key anaerobic taxa at multiple time-points, including Clostridium cluster XIVa and IV taxa. The metabolomic data also showed delayed recovery in recurrent participants, and moreover mapped to pathways suggesting distinct functional abnormalities in the microbiome or host, such as decreased microbial deconjugation activity, lowered levels of endocannabinoids, and elevated markers of host cell damage. Further, using predictive statistical/machine learning models, we demonstrated that the metabolomic data, but not the other data sources, can accurately predict future recurrence at 1 week (AUC 0.77 [0.71, 0.86; 95% interval]) and 2 weeks (AUC 0.77 [0.69, 0.85; 95% interval]) post-treatment for primary CDI.ConclusionsThe prospective, longitudinal, and multi-omic nature of our CDI recurrence study allowed us to uncover previously unrecognized dynamics in the microbiome and host presaging recurrence, and, in particular, to elucidate changes in the understudied gut metabolome. Moreover, we demonstrated that a small set of metabolites can accurately predict future recurrence. Our findings have implications for development of diagnostic tests and treatments that could ultimately short-circuit the cycle of CDI recurrence, by providing candidate metabolic biomarkers for diagnostics development, as well as offering insights into the complex microbial and metabolic alterations that are protective or permissive for recurrence.9zdFyUsMbXbMuCAdFKvo9qVideo

In vitro gastrointestinal digestion of Lentinus squarrosulus powder and impact on human fecal microbiota

Humans have long-used mushrooms as food and medicine, but digestion and colonic fermentation of most mushrooms, including Lentinus squarrosulus is markedly unknown. Here, nutritional profile, digestion and colonic fermentation of L. squarrosulus powder (LP) were determined. The powder contained mainly carbohydrate and protein. SEM and F-TIR analysis of the resistant hydrolysate (RH) revealed that the structure and ratio of carbohydrate and protein components were altered, and released known immunomodulation agents; beta-glucans and mannose. Both LP and RH promoted selected probiotic bacteria, especially Bifidobacterium strains. Using fecal microbiota of five volunteers (V1, V2, V3, V4 and V5), RH stimulated the microbiota of all used volunteers, via decreasing the ratio of Firmicutes/Bacteroidetes ranging from 1.3 to 8.2 times. Also, RH increased the relative abundance of vital immunomodulators; Bacteroides, Bifidobacterium, Clostridium cluster XIVa and IV, and Sutterella. Additionally, RH fermentation enriched the content of branch-chain fatty acids (BCFA) and short-chain fatty acids (SCFA), indicating protein and carbohydrate usage. Notably, propionic and butyric acids were abundant in V1, V2 and V3, while in V4 and V5, acetic and butyric acids were most enriched. Suggesting L. squarrosulus as functional mushroom to improve health and prevent diseases by enhancing gut health.

Development of Alcohol-Associated Hepatitis Is Associated With Specific Changes in Gut-Modified Bile Acids.

The perturbations in bile acids (BAs) in alcohol‐associated hepatitis (AH) and its relationship to disease severity is not well defined. The aims of this study were to define (1) the effects of heavy alcohol consumption on BAs and related microbiome, (2) the additional changes with AH, and (3) the relationship of these changes to disease severity. In this multicenter study, plasma and fecal BAs and related microbiome were interrogated in healthy individuals, heavy drinking controls (HDCs) without overt liver disease, and AH. Compared to healthy controls, HDCs had increased glycine‐conjugated 7α and 27α primary BAs and increased secondary BA glycocholenic sulfate (multiple‐comparison adjusted P < 0.05 for all). Plasma‐conjugated cholic and chenodeoxycholic acid increased in AH along with the secondary BAs ursodeoxycholic and lithocholic acid (P < 0.001 for all), whereas deoxycholic acid decreased; however fecal concentrations of both deoxycholic acid and lithocholic acid were decreased. Glycocholenic acid further increased significantly from HDCs to AH. HDCs and AH had distinct plasma and fecal BA profiles (area under the curve, 0.99 and 0.93, respectively). Plasma taurochenodeoxycholic acid and tauroursodeoxycholic acid were directly related to disease severity, whereas fecal ursodeoxycholic acid was inversely related. The fecal abundance of multiple taxa involved in formation of secondary BAs, especially deoxycholic acid (Clostridium cluster XIVa) was decreased in AH. Multiple genera containing taxa expressing 3α, 3β, 7α, and 7β epimerases were decreased with concordant changes in fecal BAs that required these functions for formation. Conclusion: There are distinct changes in BA‐transforming microbiota and corresponding BAs in AH that are related to disease severity.

Divergent functions of IL-17-family cytokines in DSS colitis: Insights from a naturally-occurring human mutation in IL-17F.

The IL-17 family is structurally distinct from other cytokine subclasses. IL-17A and IL-17F, the most closely related of this family, form homodimers and an IL-17AF heterodimer. While IL-17A and IL-17F exhibit similar activities in many settings, in others their functions are divergent. To better understand the function of IL-17F in vivo, we created mice harboring a mutation in Il17f originally described in humans with unexplained chronic mucosal candidiasis (Ser-65-Leu). We evaluated Il17fS65L/S65L mice in DSS-colitis, as this is one of the few settings where IL-17A and IL-17F exhibit opposing activities. Specifically, IL-17A is protective of the gut epithelium, a finding that was revealed when trials of anti-IL-17A biologics in Crohn's disease failed and recapitulated in many mouse models of colitis. In contrast, mice lacking IL-17F are resistant to DSS-colitis, partly attributable to alterations in intestinal microbiota that mobilize Tregs. Here we report that Il17fS65L/S65L mice do not phenocopy Il17f-/- mice in DSS colitis, but rather exhibited a worsening disease phenotype much like Il17a-/- mice. Gut inflammation in Il17fS65L/S65L mice correlated with reduced Treg accumulation and lowered intestinal levels of Clostridium cluster XIV. Unexpectedly, the protective DSS-colitis phenotype in Il17f-/- mice could be reversed upon co-housing with Il17fS65L/S65L mice, also correlating with Clostridium cluster XIV levels in gut. Thus, the Il17fS65L/S65L phenotype resembles an IL-17A deficiency more closely than IL-17F deficiency in the setting of DSS colitis.

Effects of Zinc Source and Enzyme Addition on the Fecal Microbiota of Dogs.

Supplemental zinc from organic sources has been suggested to be more bioavailable than inorganic ones for dog foods. However, the bioavailability of zinc might be affected by dietary constituents such as phytates. The present study aimed to evaluate the effects of two zinc sources (zinc sulfate and zinc proteinate) and the addition of a multi-enzymatic complex from the solid-state fermentation of Aspergillus niger on end-products of fecal fermentation and fecal microbiota of adult Beagles fed a high-phytate diet. The experimental design consisted of three 4 × 4 Latin Squares with a 2 × 2 factorial arrangement of treatments (n = 12 Beagles), with four periods and four diets: zinc sulfate without (IZ) or with (IZ +) enzyme addition, and zinc proteinate without (OZ) or with (OZ +) enzyme addition. Enzyme addition significantly affected Faith’s phylogenetic diversity index, whereas zinc source did not affect either beta or alpha diversity measures. Linear discriminant analysis effect size detected nine taxa as markers for organic zinc, 18 for inorganic source, and none for enzyme addition. However, with the use of a negative binomial generalized linear model, further effects were observed. Organic zinc was associated with a significantly higher abundance of Firmicutes and lower Proteobacteria and Bacteroidetes, although at a genus level, the response varied. The DNA abundance of Clostridium cluster I, Clostridium cluster XIV, Campylobacter spp., Ruminococcaceae, Turicibacter, and Blautia was significantly higher in dogs fed IZ and IZ + diets. Higher abundance of genus Lactobacillus was observed in dogs fed enzyme-supplemented diets. End-products of fecal fermentation were not affected by zinc source or enzymes. An increase in some taxa of the phyla Actinobacteria and Firmicutes was observed in feces of dogs fed organic zinc with enzyme addition but not with inorganic zinc. This study fills a gap in knowledge regarding the effect of zinc source and enzyme addition on the fecal microbiota of dogs. An association of zinc bioavailability and bacteria abundance is suggested, but the implications for the host (dog) are not clear. Further studies are required to unveil the effects of the interaction between zinc sources and enzyme addition on the fecal microbial community.