Manipulation Of Microbiota Research Articles

Integrated multi-omics reveals the roles of cecal microbiota and its derived bacterial consortium in promoting chicken growth.

The improvement of chicken growth performance is one of the major concerns for the poultry industry. Gut microbes are increasingly evidenced to be associated with chicken physiology and metabolism, thereby influencing chicken growth and development. Here, through integrated multi-omics analyses, we showed that chickens from the same line differing in their body weight were very different in their gut microbiota structure and host-microbiota crosstalk; microbes in high body weight (HBW) chickens contributed to chicken growth by regulating the gut function and homeostasis. We also verified that a specific bacterial consortium consisting of isolates from the HBW chickens has the potential to be used as chicken growth promoters. These findings provide new insights into the potential links between gut microbiota and chicken phenotypes, shedding light on future manipulation of chicken gut microbiota to improve chicken growth performance.

Will the manipulation of the gut microbiota be effective for the treatment of metabolic diseases?

Will the manipulation of the gut microbiota be effective for the treatment of metabolic diseases?

Effect of inulin supplementation on clinical symptoms, inflammatory and oxidative stress markers in women with migraine: study protocol for a randomized clinical trial

BackgroundMigraine is a complex, chronic, and debilitating multifactorial disorder characterized by recurrent episodes of headache and related symptoms. It typically begins in early ages and is more prevalent in women than in men. Recently, the gut–brain axis has emerged as a new candidate that may be linked to neurological diseases. We hypothesize that selective modulation of the intestinal microbiota, oxidative stress, and inflammation through inulin supplementation may improve clinical outcomes in these patients. Therefore, this study aims to examine the effects of high-performance inulin supplementation on clinical symptoms, mental health, quality of life (QOL), intestinal permeability, and inflammatory and oxidative stress factors in women with migraine.MethodsThis is a randomized, double-blind, placebo-controlled clinical trial involving 80 women with migraine who meet the inclusion criteria (aged between 20 and 50 years with a diagnosis of migraine by a neurologist based on the ICDH-3). Participants will be assigned to receive a daily dose of 10 g of inulin for 12 weeks (intervention group, n = 40) or 10 g of maltodextrin as a placebo for the same duration (control group, n = 40). The primary outcome will measure the variations in the frequency of headache experienced by the patients. Secondary outcomes will encompass serum levels of zonulin, high-sensitive C-reactive protein, total antioxidant capacity, total oxidant status, nitric oxide, mental status, QOL, duration, and severity of migraine attacks.DiscussionThis clinical trial aims to evaluate the effect of inulin supplementation on inflammatory status, oxidative stress, intestinal permeability, clinical symptoms, mental health, and QOL in women with migraine. The findings of this trial could contribute to the identification of mechanistic action and evidence-based clinical guidelines that address gut microbiota manipulation to maximize health benefits in the management of clinical outcomes in migraine patients.Trial registrationIranian Registry of Clinical Trials (www.irct.ir) (ID: IRCT20121216011763N58). Registration date: 23 April 2023.Trial statusThe protocol is version 3.0, September 17, 2023. Recruitment began August 21, 2023, and is anticipated to be completed by March 22, 2024.

Effects of different feeding systems on ruminal fermentation, digestibility, methane emissions, and microbiota of Hanwoo steers.

This study evaluates how different feeding systems impact ruminal fermentation, methane production, and microbiota of Hanwoo steers native to Korea. In a replicated 2 × 2 crossover design over 29 days per period, eight Hanwoo steers (507.1 ± 67.4 kg) were fed twice daily using a separate feeding (SF) system comprising separate concentrate mix and forage or total mixed rations (TMR) in a 15:85 ratio. The TMR-feeding group exhibited a considerable neutral detergent fiber digestibility increase than the SF group. However, ruminal fermentation parameters and methane production did not differ between two feeding strategies. In addition, TMR-fed steers expressed elevated Prevotellaceae family, Christensenellaceae R-7 group, and an unidentified Veillonellaceae family genus abundance in their rumen, whereas SF-fed steers were rich in the Rikenellaceae RC9 gut group, Erysipelotrichaceae UCG-004, and Succinivibrio. Through linear regression modeling, positive correlations were observed between the Shannon Diversity Index and the SF group's dry matter intake and methane production. Although feeding systems do not affect methane production, they can alter ruminal microbes. These results may guide future feeding system investigations or ruminal microbiota manipulations as a methane-mitigation practice examining different feed ingredients.

Immune checkpoint inhibitor-induced colitis is mediated by polyfunctional lymphocytes and is dependent on an IL23/IFNγ axis

Immune checkpoint inhibitors (CPIs) are a relatively newly licenced cancer treatment, which make a once previously untreatable disease now amenable to a potential cure. Combination regimens of anti-CTLA4 and anti-PD-1 show enhanced efficacy but are prone to off-target immune-mediated tissue injury, particularly at the barrier surfaces. To probe the impact of immune checkpoints on intestinal homoeostasis, mice are challenged with anti-CTLA4 and anti-PD-1 immunotherapy and manipulation of the intestinal microbiota. The immune profile of the colon of these mice with CPI-colitis is analysed using bulk RNA sequencing, single-cell RNA sequencing and flow cytometry. CPI-colitis in mice is dependent on the composition of the intestinal microbiota and by the induction of lymphocytes expressing interferon-γ (IFNγ), cytotoxicity molecules and other pro-inflammatory cytokines/chemokines. This pre-clinical model of CPI-colitis could be attenuated following blockade of the IL23/IFNγ axis. Therapeutic targeting of IFNγ-producing lymphocytes or regulatory networks, may hold the key to reversing CPI-colitis.

Meta-analysis reveals the predictable dynamic development of the gut microbiota in commercial pigs.

Understanding the mechanisms of microbiome assembly during host development is crucial for successful modulation of the gut microbiome to improve host health and growth. However, results from previous microbial intervention studies to improve swine growth have largely been inconsistent due to the constantly changing nature of the gut microbiota and limited longitudinal sampling. Detailed characterization of the swine gut microbiota through meta-analysis allows us to understand the dynamics of microbial community succession, as well as the transient and natural variations between time points and animals. A total of 3,313 fecal microbial communities from over 349 pigs covering 60 time points (from birth to market age) from 14 publications were included in this meta-analysis. Despite differences in animal breeds and management, generalizable patterns of community assembly were identified. Alpha diversity continuously increased during early stages of animal growth and more slowly in the later stages. Beta regression analysis revealed that more microbial taxa were enriched, while fewer were excluded by the gut microbiota. The microbial community structure also changed significantly between days at early ages and became more similar as pigs aged, as revealed by dissimilarity and distance metrics. Dirichlet multinomial mixtures analysis supported gradient microbial clustering in longitudinal pig fecal samples, and we found that the early samples spread to more clusters than those from older pigs. Random forest regression identified 30 operational taxonomic units as potential microbial biomarkers for modeling swine gut microbiota development. External validation showed this model could be generalized to future microbiome studies conducted in suckling and weaning pigs and adds to the toolkit to quantify community succession. IMPORTANCE The swine gut microbiome undergoes an age-dependent assembly pattern with a developmental phase at early ages and a stabilization phase at later ages. Shorter time intervals and a wider range of data sources provided a clearer understanding of the gut microbiota colonization and succession and their associations with pig growth and development. The rapidly changing microbiota of suckling and weaning pigs implies potential time targets for growth and health regulation through gut microbiota manipulation. Since swine gut microbiota development is predictable, swine microbiota age can be calculated and compared between animal treatment groups rather than relying only on static time-matched comparisons.

P-Cresol Sulfate Is a Sensitive Urinary Marker of Fecal Microbiota Transplantation and Antibiotics Treatments in Human Patients and Mouse Models.

Fecal microbiota transplantation (FMT) has emerged as a highly effective therapy for recurrent Clostridioides difficile infection (rCDI) and also a potential therapy for other diseases associated with dysbiotic gut microbiota. Monitoring metabolic changes in biofluids and excreta is a noninvasive approach to identify the biomarkers of microbial recolonization and to understand the metabolic influences of FMT on the host. In this study, the pre-FMT and post FMT urine samples from 11 rCDI patients were compared through metabolomic analyses for FMT-induced metabolic changes. The results showed that p-cresol sulfate in urine, a microbial metabolite of tyrosine, was rapidly elevated by FMT and much more responsive than other microbial metabolites of aromatic amino acids (AAAs). Because patients were treated with vancomycin prior to FMT, the influence of vancomycin on the microbial metabolism of AAAs was examined in a mouse feeding trial, in which the decreases in p-cresol sulfate, phenylacetylglycine, and indoxyl sulfate in urine were accompanied with significant increases in their AAA precursors in feces. The inhibitory effects of antibiotics and the recovering effects of FMT on the microbial metabolism of AAAs were further validated in a mouse model of FMT. Overall, urinary p-cresol sulfate may function as a sensitive and convenient therapeutic indicator on the effectiveness of antibiotics and FMT for the desired manipulation of gut microbiota in human patients.

Multi-breed host rumen epithelium transcriptome and microbiome associations and their relationship with beef cattle feed efficiency

Understanding host-microbial interactions in the rumen and its influence on desirable production traits may lead to potential microbiota manipulation or genetic selection for improved cattle feed efficiency. This study investigated the host transcriptome and its correlation with the rumen archaea and bacteria differential abundance of two pure beef cattle breeds (Angus and Charolais) and one composite beef hybrid (Kinsella) divergent for residual feed intake (RFI; low-RFI vs. high-RFI). Using RNA-Sequencing of rumen tissue and 16S rRNA gene amplicon sequencing, differentially expressed genes (FDR ≤ 0.05, |log2(Fold-change) >|2) and differentially abundant (p-value < 0.05) archaea and bacteria amplicon sequence variants (ASV) were determined. Significant correlations between gene expression and ASVs (p-value < 0.05) were determine using Spearman correlation. Interesting associations with muscle contraction and the modulation of the immune system were observed for the genes correlated with bacterial ASVs. Potential functional candidate genes for feed efficiency status were identified for Angus (CCL17, CCR3, and CXCL10), Charolais (KCNK9, GGT1 and IL6), and Kinsella breed (ESR2). The results obtained here provide more insights regarding the applicability of target host and rumen microbial traits for the selection and breeding of more feed efficient beef cattle.

The Effect of Maternal Probiotic or Synbiotic Supplementation on Sow and Offspring Gastrointestinal Microbiota, Health, and Performance.

The increasing prevalence of antimicrobial-resistant pathogens has prompted the reduction in antibiotic and antimicrobial use in commercial pig production. This has led to increased research efforts to identify alternative dietary interventions to support the health and development of the pig. The crucial role of the GIT microbiota in animal health and performance is becoming increasingly evident. Hence, promoting an improved GIT microbiota, particularly the pioneer microbiota in the young pig, is a fundamental focus. Recent research has indicated that the sow's GIT microbiota is a significant contributor to the development of the offspring's microbiota. Thus, dietary manipulation of the sow's microbiota with probiotics or synbiotics, before farrowing and during lactation, is a compelling area of exploration. This review aims to identify the potential health benefits of maternal probiotic or synbiotic supplementation to both the sow and her offspring and to explore their possible modes of action. Finally, the results of maternal sow probiotic and synbiotic supplementation studies are collated and summarized. Maternal probiotic or synbiotic supplementation offers an effective strategy to modulate the sow's microbiota and thereby enhance the formation of a health-promoting pioneer microbiota in the offspring. In addition, this strategy can potentially reduce oxidative stress and inflammation in the sow and her offspring, enhance the immune potential of the milk, the immune system development in the offspring, and the sow's feed intake during lactation. Although many studies have used probiotics in the maternal sow diet, the most effective probiotic or probiotic blends remain unclear. To this extent, further direct comparative investigations using different probiotics are warranted to advance the current understanding in this area. Moreover, the number of investigations supplementing synbiotics in the maternal sow diet is limited and is an area where further exploration is warranted.

Genetically engineered Lactobacillus paracasei rescues colonic angiotensin converting enzyme 2 (ACE2) and attenuates hypertension in female Ace2 knock out rats

Engineered gut microbiota represents a new frontier in medicine, in part serving as a vehicle for the delivery of therapeutic biologics to treat a range of host conditions. The gut microbiota plays a significant role in blood pressure regulation; thus, manipulation of gut microbiota is a promising avenue for hypertension treatment. In this study, we tested the potential of Lactobacillus paracasei, genetically engineered to produce and deliver human angiotensin converting enzyme 2 (Lacto-hACE2), to regulate blood pressure in a rat model of hypertension with genetic ablation of endogenous Ace2 (Ace2-/- and Ace2-/y). Our findings reveal a sex-specific reduction in blood pressure in female (Ace2-/-) but not male (Ace2-/y) rats following colonization with the Lacto-hACE2. This beneficial effect of lowering blood pressure was aligned with a specific reduction in colonic angiotensin II, but not renal angiotensin II, suggesting the importance of colonic Ace2 in the regulation of blood pressure. We conclude that this approach of targeting the colon with engineered bacteria for delivery of ACE2 represents a promising new paradigm in the development of antihypertensive therapeutics.

Inulin-type fructans and 2’fucosyllactose alter both microbial composition and appear to alleviate stress-induced mood state in a working population compared to placebo (maltodextrin): the EFFICAD Trial, a randomized, controlled trial

BackgroundThere is increasing interest in the bidirectional relationship existing between the gut and brain and the effects of both oligofructose and 2’fucosyllactose to alter microbial composition and mood state. Yet, much remains unknown about the ability of oligofructose and 2’fucosyllactose to improve mood state via targeted manipulation of the gut microbiota. ObjectivesWe aimed to compare the effects of oligofructose and 2’fucosyllactose alone and in combination against maltodextrin (comparator) on microbial composition and mood state in a working population. MethodsWe conducted a 5-wk, 4-arm, parallel, double-blind, randomized, placebo-controlled trial in 92 healthy adults with mild-to-moderate levels of anxiety and depression. Subjects were randomized to oligofructose 8 g/d (plus 2 g/d maltodextrin); maltodextrin 10 g/d; oligofructose 8 g/d plus 2’fucosyllactose (2 g/d) or 2’fucosyllactose 2 g/d (plus 8 g/d maltodextrin). Changes in microbial load (fluorescence in situ hybridization-flow cytometry) and composition (16S ribosomal RNA sequencing) were the primary outcomes. Secondary outcomes included gastrointestinal sensations, bowel habits, and mood state parameters. ResultsThere were significant increases in several bacterial taxa including Bifidobacterium, Bacteroides, Roseburia, and Faecalibacterium prausnitzii in both the oligofructose and oligofructose/2’fucosyllactose interventions (all P ≤ 0.05). Changes in bacterial taxa were highly heterogenous upon 2’fuscoyllactose supplementation. Significant improvements in Beck Depression Inventory, State Trait Anxiety Inventory Y1 and Y2, and Positive and Negative Affect Schedule scores and cortisol awakening response were detected across oligofructose, 2’fucosyllactose, and oligofructose/2’fucosyllactose combination interventions (all P ≤ 0.05). Both sole oligofructose and oligofructose/2’fuscosyllactose combination interventions outperformed both sole 2’fucosyllactose and maltodextrin in improvements in several mood state parameters (all P ≤ 0.05). ConclusionThe results of this study indicate that oligofructose and combination of oligofructose/2’fucosyllactose can beneficially alter microbial composition along with improving mood state parameters. Future work is needed to understand key microbial differences separating individual responses to 2’fucosyllactose supplementation.This trial was registered at clinicaltrials.gov as NCT05212545.

A Distinct Nasal Microbiota Signature in Peritoneal Dialysis Patients.

The nasal passages harbor both commensal and pathogenic bacteria and can be associated with infectious complications. The nasal microbiome in peritoneal dialysis (PD) patients, however, has not been well characterized. In this study, we sought to characterize the anterior nasal microbiota in peritoneal dialysis (PD) patients and assess its association with PD peritonitis. In this study, we recruited 32 PD patients, 37 kidney transplant (KTx) recipients, and 22 living donor/healthy control (HC) participants and collected their anterior nasal swabs at a single point in time. We followed the PD patients for future development of peritonitis. We performed 16S rRNA gene sequencing of the V4-V5 hypervariable region to determine the nasal microbiota. We compared nasal abundance of common genera among the 3 groups using Wilcoxon rank sum testing with Benjamini-Hochberg adjustment. DESeq2 was also utilized to compare the groups at the amplicon sequence variant levels. In the entire cohort, the most abundant genera in the nasal microbiota included: Staphylococcus, Corynebacterium, Streptococcus, and Anaerococcus. Correlational analyses revealed a significant inverse relationship between the nasal abundance of Staphylococcus and that of Corynebacterium. PD patients have a higher nasal abundance of Streptococcus than KTx recipients and HC participants. PD patients have a more diverse representation of Staphylococcus and Streptococcus than KTx recipients and HC participants. PD patients who concurrently have or who developed future Staphylococcus peritonitis had a numerically higher nasal abundance of Staphylococcus than PD patients who did not develop Staphylococcus peritonitis. We find a distinct nasal microbiota signature in PD patients compared to KTx recipients and HC participants. Given the potential relationship between the nasal pathogenic bacteria and infectious complications, further studies are needed to define the nasal microbiota associated with these infectious complications and to conduct studies on the manipulation of the nasal microbiota to prevent such complications.

Exploring the complex role of gut microbiome in the development of precision medicine strategies for targeting microbial imbalance-induced colon cancer.

The gut microbiome has been increasingly recognized as a key player in the development and progression of colon cancer. Alterations in the gut microbiota, known as dysbiosis, can lead to a variety of medical issues. Microbial adaptation through signals and small molecules can enhance pathogen colonization and modulate host immunity, significantly impacting disease progression. Quorum sensing peptides and molecules have been linked to the progression of colon cancer. Various interventions, such as fecal microbiota transplantation, probiotics, prebiotics, synbiotics, and antibiotics, have been used to reverse dysbiosis with mixed results and potential side effects. Thus, a personalized approach to treatment selection based on patient characteristics, such as individual gut microbiota manipulation, is necessary to prevent and treat diseases like colon cancer. With advances in metagenomic sequencing and other omics technologies, there has been a growing interest in developing precision medicine strategies for microbial imbalance-induced colon cancer. This review serves as a comprehensive synthesis of current knowledge on the gut microbiome involvement in colon cancer. By exploring the potential of utilizing the gut microbiome as a target for precision medicine, this review underscores the exciting opportunities that lie ahead. Although challenges exist, the integration of microbiome data into precision medicine approaches has the potential to revolutionize the management of colon cancer, providing patients with more personalized and effective treatment options.

Recipient-independent, high-accuracy FMT-response prediction and optimization in mice and humans

BackgroundSome microbiota compositions are associated with negative outcomes, including among others, obesity, allergies, and the failure to respond to treatment. Microbiota manipulation or supplementation can restore a community associated with a healthy condition. Such interventions are typically probiotics or fecal microbiota transplantation (FMT). FMT donor selection is currently based on donor phenotype, rather than the anticipated microbiota composition in the recipient and associated health benefits. However, the donor and post-transplant recipient conditions differ drastically. We here propose an algorithm to identify ideal donors and predict the expected outcome of FMT based on donor microbiome alone. We also demonstrate how to optimize FMT for different required outcomes.ResultsWe show, using multiple microbiome properties, that donor and post-transplant recipient microbiota differ widely and propose a tool to predict the recipient post-transplant condition (engraftment success and clinical outcome), using only the donors’ microbiome and, when available, demographics for transplantations from humans to either mice or other humans (with or without antibiotic pre-treatment). We validated the predictor using a de novo FMT experiment highlighting the possibility of choosing transplants that optimize an array of required goals.We then extend the method to characterize a best-planned transplant (bacterial cocktail) by combining the predictor and a generative genetic algorithm (GA). We further show that a limited number of taxa is enough for an FMT to produce a desired microbiome or phenotype.ConclusionsOff-the-shelf FMT requires recipient-independent optimized FMT selection. Such a transplant can be from an optimal donor or from a cultured set of microbes. We have here shown the feasibility of both types of manipulations in mouse and human recipients.1xEPDcpaMv3Ywip7BmLU-XVideo

Cervicovaginal Microbial-Immune State and Group B Streptococcus Colonization in Pregnancy.

Maternal colonization with Group B Streptococcus (GBS) is a significant risk factor for serious neonatal morbidity. There are limited data on how the cervicovaginal (CV) microbiota and host immune factor β-defensin-2 might influence GBS colonization in pregnant individuals. This study sought to determine if the CV microbiota is associated with GBS colonization in pregnant individuals, and if β-defensin-2 modifies this relationship. This was a secondary analysis of a prospective cohort study of pregnant individuals with singleton pregnancies who had CV microbiota specimens analyzed at 16 to 20, 20 to 24, and 24 to 28 weeks' gestation, along with a third trimester GBS rectovaginal (RV) culture (n = 492). Microbiota data were analyzed with 16S rRNA gene sequencing and classified into community state types (CSTs). Log-binomial multivariable regression was used to model associations between CST and GBS RV status and to calculate risk ratios. β-defensin-2, an immune factor known to modulate the relationship between CST and pregnancy outcomes, was examined as an effect modifier. Of 492 individuals, 34.3% were GBS RV + . Compared with individuals with CST I at 16 to 20 weeks, individuals with CST IV-A and CST II had a significantly elevated relative risk of subsequent GBS RV+ status. When stratified by high and low β-defensin-2 levels, β-defensin-2 was found to be an effect modifier of the association between CST IV-A and GBS RV+ status. In individuals with low β-defensin-2 levels, CST VI-A was associated with GBS RV+ status, but among individuals with high β-defensin-2 levels, there was no such association (interaction p-value = 0.03). Pregnant individuals with CV microbiota characterized by CST IV-A and CST II had significantly elevated risk of GBS RV colonization in the third trimester compared with those with CST I, and β-defensin-2 was an effect modifier of the association between CST IV-A and GBS RV+ status. Future research should investigate if manipulation of the CV microbiota can prevent GBS colonization, thereby reducing intrapartum antibiotic prophylaxis and the risks of neonatal GBS infection. · The relationship between the CV microbiota and GBS RV colonization is unknown.. · A Lactobacillus-deficient, anaerobic rich vaginal community, CST IV-A, is associated with increased risk of GBS RV colonization.. · β-defensin-2 is an effect modifier of the association between CST IV-A and GBS RV+ status..

Postbiotics in oncology: science or science fiction?

The gut microbiome has been increasingly understood to play a critical role in carcinogenesis and cancer disease progression. The most recent research advancements have shown that different tools of microbiota manipulation contribute to gut microbiome-immune-oncology axis modulation, offering exciting opportunities for targeted interventions aimed at improving the efficacy of established anti-cancer therapy. Postbiotics are a new entry among the biotics showing beneficial effects on human health while not requiring living cells to obtain the health effect and therefore not subjected to food safety rules for live microorganisms. Postbiotics are recently defined as the "preparation of inanimate microorganisms and/or their components that confers a health benefit on the host" and have gradually become the focus of the scientific community. Since the beginning of research on this topic, numerous studies about postbiotics have been proven to strengthen the gut barrier, reduce inflammation, and promote antimicrobial activity. However, research on the potential application of cancer therapy is still at the early stages of its efforts to uncover all the secrets surrounding postbiotics. This review aims to increase our understanding of the anti-cancer effect of postbiotics throughout a "bibliographic journey" on the biological activity of their components, including exopolysaccharides, cell wall fragments, tryptophan metabolites, enzymes, bacterial lysates, extracellular vesicles, and short-chain fatty acids, highlighting their perspective as a new supportive therapeutic method of treatment and identifying the literature gaps where further research is needed.

Effects of synbiotic supplementation on intestinal microbiota composition in children and adolescents with exogenous obesity: (Probesity-2 trial)

IntroductionGut microbiota manipulation may be a potential therapeutic target to reduce host energy storage. There is limited information about the effects of probiotics/synbiotics on intestinal microbiota composition in children and adolescents with obesity. The objective of this randomized double-blind placebo-controlled trial was to test the effects of a multispecies synbiotic on intestinal microbiota composition in children and adolescents with exogenous obesity.MethodChildren with exogenous obesity were managed with a standard diet and increased physical activity and were randomly allocated into two groups at a ratio of 1:1; the 1st group received synbiotic supplementation (probiotic mixture including Lactobacillus acidophilus, Lacticaseibacillus. rhamnosus, Bifidobacterium bifidum, Bifidobacterium longum, Enterococcus faecium (total 2.5 × 109 CFU/sachet) and fructo-oligosaccharides (FOS; 625 mg/sachet) for 12 weeks; the 2nd group received placebo once daily for 12 weeks. Fecal samples were obtained before and at the end of the 12-week intervention to characterize the changes in the gut microbiota composition. Detailed metagenomic and bioinformatics analyses were performed.ResultsBefore the intervention, there were no significant differences in alpha diversity indicators between the synbiotic and placebo groups. After 12 weeks of intervention, the observed taxonomic units and Chao 1 were lower in the synbiotic group than at baseline (p < 0.001 for both). No difference for alpha diversity indicators was observed in the placebo group between baseline and 12 weeks of intervention. At the phylum level, the intestinal microbiota composition of the study groups was similar at baseline. The major phyla in the synbiotic group were Firmicutes (66.7%) and Bacteroidetes (18.8%). In the synbiotic group, the Bacteroidetes phylum was higher after 12 weeks than at baseline (24.0% vs. 18.8%, p < 0.01). In the synbiotic group, the Firmicutes/Bacteroidetes ratio was 3.54 at baseline and 2.75 at 12 weeks of intervention (p < 0.05). In the placebo group, the Firmicutes/Bacteroidetes ratio was 4.70 at baseline and 3.54 at 12 weeks of intervention (p < 0.05). After 12 weeks of intervention, the Firmicutes/Bacteroidetes ratio was also lower in the synbiotic group than in the placebo group (p < 0.05). In the synbiotic group, compared with the baseline, we observed a statistically significant increase in the genera Prevotella (5.28–14.4%, p < 0.001) and Dialister (9.68–13.4%; p < 0.05). Compared to baseline, we observed a statistically significant increase in the genera Prevotella (6.4–12.4%, p < 0.01) and Oscillospira (4.95% vs. 5.70%, p < 0.001) in the placebo group. In the synbiotic group, at the end of the intervention, an increase in Prevotella, Coprococcus, Lachnospiraceae (at the genus level) and Prevotella copri, Coprococcus eutactus, Ruminococcus spp. at the species level compared to baseline (predominance of Eubacterium dolichum, Lactobacillus ruminis, Clostridium ramosum, Bulleidia moorei) was observed. At the end of the 12th week of the study, when the synbiotic and placebo groups were compared, Bacteroides eggerthi species were dominant in the placebo group, while Collinsella stercoris species were dominant in the synbiotic group.ConclusionThis study is the first pediatric obesity study to show that a synbiotic treatment is associated with both changes intestinal microbiota composition and decreases in BMI. Trial identifier: NCT05162209 (www.clinicaltrials.gov).

Gut Microbiota and its Metabolites: Bridge of Dietary Nutrients and Alzheimer's Disease.

Alzheimer's disease (AD) is a neurodegenerative disease characterized by progressive cognitive impairment and neuroinflammation. Recent research has revealed the crucial role of gut microbiota and microbial metabolites in modulating AD. However, the mechanisms by which the microbiome and microbial metabolites affect brain function remain poorly understood. Here, we review the literature on changes in the diversity and composition of the gut microbiome in patients with AD and in animal models of AD. We also discuss the latest progress in understanding the pathways by which the gut microbiota and microbial metabolites from the host or diet regulate AD. By understanding the effects of dietary components on brain function, microbiota composition, and microbial metabolites, we examine the potential for manipulation of the gut microbiota through dietary intervention to delay the progression of AD. Although it is challenging to translate our understanding of microbiome-based approaches to dietary guidelines or clinical therapies, these findings provide an attractive target for promoting brain function.

Transmission of fungi and protozoa under grazing conditions from lactating yaks to sucking yak calves in early life

Microbiota from mothers is an essential source of microbes in early-life rumen microbiota, but the contribution of microbiota from different maternal sites to the rumen microbiota establishment in neonates needs more data. To fill this gap, we collected samples from the mouth, teat skin, and rumen of lactating yaks and from the rumen of sucking calves concomitantly on seven occasions between days 7 and 180 after birth under grazing conditions. We observed that the eukaryotic communities clustered based on sample sites, except for the protozoal community in the teat skin, with negative correlations between fungal and protozoal diversities in the rumen of calves. Furthermore, fungi in the dam’s mouth, which is the greatest source of the calf’s rumen fungi, accounted for only 0.1%, and the contribution of the dam’s rumen to the calf’s rumen fungi decreased with age and even disappeared after day 60. In contrast, the average contribution of the dam’s rumen protozoa to the calf’s rumen protozoa was 3.7%, and the contributions from the dam’s teat skin (from 0.7 to 2.7%) and mouth (from 0.4 to 3.3%) increased with age. Thus, the divergence in dam-to-calf transmissibility between fungi and protozoa indicates that the foundation of these eukaryotic communities is shaped by different rules. This study provides the first measurements of the maternal contribution to the fungal and protozoal establishment in the rumen of sucking and grazing yak calves in early life, which could be beneficial for future microbiota manipulation in neonatal ruminants.Key points• Dam to calf transfer of rumen eukaryotes occurs from multiple body sites.• A minor proportion of rumen fungi in calves originated from maternal sites.• The inter-generation transmission between rumen fungi and protozoa differs.

Faecal microbiota composition is related to response to CDK4/6-inhibitors in metastatic breast cancer: A prospective cross-sectional exploratory study

BackgroundCyclin-dependent kinase (CDK)4/6-inhibitors with endocrine therapy represent the standard of treatment of hormone receptor-positive(HR+)/human epidermal growth factor receptor 2 (HER2)-negative metastatic breast cancer (MBC). Gut microbiota seems to predict treatment response in several tumour types, being directly implied in chemotherapy resistance and development of adverse effects. No evidence is available on gut microbiota impact on efficacy of HR+ breast cancer treatment. Patients and methodsWe assessed the potential association among faecal microbiota and therapeutic efficacy of CDK4/6-inhibitors on 14 MBC patients classified as responders (R) and non-responders (NR) according to progression-free survival. A stool sample was collected at baseline and V3–V4 16S targeted sequencing was employed to assess its bacterial composition. Statistical associations with R and NR were studied. ResultsNo significant differences were observed between R and NR in terms of α-/β-diversity at the phylum and species level. Machine-learning (ML) algorithms evidenced four bacterial species as a discriminant for R (Bifidobacterium longum, Ruminococcus callidus) and NR (Clostridium innocuum, Schaalia odontolytica), and an area under curve (AUC) of 0.946 after Random Forest modelling. Network analysis evidenced two major clusters of bacterial species, named Species Interacting Groups (SIG)1–2, with SIG1 harbouring 75% of NR-related bacterial species, and SIG2 regrouping 76% of R-related species (p < 0.001). Cross-correlations among several patients’ circulating immune cells or biomarkers and bacterial species’ relative abundances showed associations with potential prognostic implications. ConclusionsOur results provide initial insights into the gut microbiota involvement in sensitivity and/or resistance to CDK4/6-inhibitors + endocrine therapy in MBC. If confirmed in larger trials, several microbiota manipulation strategies might be hypothesised to improve response to CDK4/6-inhibitors.