Adult Microbiome Research Articles

Colchicine effects on the gut microbiome in adults with metabolic syndrome.

Obesity-induced inflammation plays a substantial role in the development of insulin resistance and type 2 diabetes. The altered gut flora in obesity can also contribute to metabolic dysregulation and systemic inflammation. However, it remains unclear how dysregulation of systemic inflammation in obesity affects the gut microbiome. We hypothesized that colchicine's systemic anti-inflammatory effects in obesity would be associated with improvements in gut microbial diversity. We conducted a secondary analysis of a double-blind randomized placebo-controlled trial, in which 40 adults with obesity, high C-reactive protein (CRP) (≥2.0 mg/L), insulin resistance (homeostatic model of insulin resistance: HOMA-IR ≥2.6 mg/L), and metabolic syndrome (MetS) were randomized to three months of colchicine 0.6 mg or placebo tablets twice daily. Serum and stool samples were collected at baseline and final visit. Gut microbiota composition was characterized from stool DNA by dual-index amplification and sequencing of 16S ribosomal RNA. Pre- and post-intervention stool samples were available for 15 colchicine- and 12 placebo-treated subjects. Circulating high sensitivity CRP (hsCRP), interleukin-6, resistin, white blood count, and neutrophils were significantly decreased in the colchicine arm as compared to placebo. However, changes in stool microbiome alpha diversity, as assessed by the Chao1, Shannon, and Pielou indices, were not significant between groups. Amplicon sequence variant counts were unchanged among all examined phyla or families. Oscillibacter was the only genus to demonstrate even a nominally significant change. Among adults with obesity and MetS, colchicine significantly improved systemic inflammation. However, this anti-inflammatory effect was not associated with significant changes in the gut microbiome. Further studies are warranted to investigate this relationship.

Effects of Dietary Interventions on Gut Microbiome in Overweight or Obese Adults: A Systematic Review of Randomized Controlled Trials

Background: It has been shown that gut microbiota dysbiosis may induce intestinal permeability, and systemic inflammation, leading to metabolic dysregulation. Furthermore, it has been implicated in the etiology of obesity. Dietary intake is known to affect the gut microbiota. These RCTs suggested that different dietary interventions may exhibit different effects on the composition of gut microbiota in overweight or obese individuals.Objectives: This systematic review aimed to determine the effect of dietary intervention on the gut microbiota profiles in overweight or obese adults. The primary outcome of this systematic review is alpha-beta diversity and its changes at the species level.Materials and Methods: This systematic review followed the PRISMA guidelines and was registered in the PROSPERO database with registration number CRD42022298891. A systematic search was conducted through the databases PubMed, MEDLINE, CINAHL, and Scopus literature using the terms: “gut microbiota”,“microbiome”,“overweight”,“obesity”, “insulin sensitivity”,“insulin resistance”,“blood glucose”,“randomized controlled trial”. After screening abstracts and full texts, 18 articles were extracted by two authors.Results: Among the 18 RCT studies, dietary intervention gave an impact on gut microbiota alpha diversity changes in four studies. However, 7 studies showed no significant changes or differences compared to the placebo group. Beta diversity analysis was reported in 7 among 11 studies that performed alpha diversity analysis. Significant changes were found in food nutrients group (fiber supplementation) studies conducted over 8-12 weeks period. Seven more studies did not report any analysis of variance in either alpha or beta diversity. Changes in the composition of gut microbiota could be observed in dietary pattern interventions and resulting in improved metabolic status, except in the fried meat group diet. Interventions with food groups, food nutrients, and probiotics did not change the composition of gut microbiota.Conclusion: The effects of dietary interventions on alpha-beta diversity are inconsistent, but rather showed more consistent effects on the changes in microbiota composition, especially in dietary pattern interventions.

Bacterial gut microbiomes of aculeate brood parasites overlap with their aculeate hosts', but have higher diversity and specialization.

Despite growing interest in gut microbiomes of aculeate Hymenoptera, research so far focused on social bees, wasps, and ants, whereas non-social taxa and their brood parasites have not received much attention. Brood parasitism, however, allows to distinguish between microbiome components horizontally transmitted by spill-over from the host with such inherited through vertical transmission by mothers. Here, we studied the bacterial gut microbiome of adults in seven aculeate species in four brood parasite-host systems: two bee-mutillid (host-parasitoid) systems, one halictid bee-cuckoo bee system, and one wasp-chrysidid cuckoo wasp system. We addressed the following questions: (1) Do closely related species possess a more similar gut microbiome? (2) Do brood parasites share components of the microbiome with their host? (3) Do brood parasites have different diversity and specialization of microbiome communities compared with the hosts? Our results indicate that the bacterial gut microbiome of the studied taxa was species-specific, yet with a limited effect of host phylogenetic relatedness and a major contribution of shared microbes between hosts and parasites. However, contrasting patterns emerged between bee-parasite systems and the wasp-parasite system. We conclude that the gut microbiome in adult brood parasites is largely affected by their host-parasite relationships and the similarity of trophic food sources between hosts and parasites.

Exploratory analysis of one versus two-day intermittent fasting protocols on the gut microbiome and plasma metabolome in adults with overweight/obesity.

Nutritional interventions are a promising therapeutic option for addressing obesity and cardiometabolic dysfunction. One such option, intermittent fasting (IF), has emerged as a viable alternative to daily caloric restriction and may beneficially modulate body weight regulation and alter the gut microbiome (GM) and plasma metabolome. This secondary analysis of a larger, registered trial (ClinicalTrials.gov ID: NCT04327141) examined the effect of a four-week intervention comparing one vs. two-consecutive days of IF in combination with protein pacing (IF-P; 4-5 meals/day, >30% protein/day) on the GM, the plasma metabolome, and associated clinical outcomes in overweight and obese adults. Participants (n = 20) were randomly assigned to either a diet consisting of one fasting day (total of 36 h) and six low-calorie P days per week (IF1-P, n = 10) or two fasting days (60 h total) and five low-calorie P days per week (IF2-P, n = 10). The fecal microbiome, clinical outcomes, and plasma metabolome were analyzed at baseline (week 0) and after four weeks. There were no significant time or interaction effects for alpha diversity; however, baseline alpha diversity was negatively correlated with percent body fat change after the four-week intervention (p = 0.030). In addition, beta-diversity for both IF groups was altered significantly by time (p = 0.001), with no significant differences between groups. The IF1-P group had a significant increase in abundance of Ruminococcaceae Incertae Sedis and Eubacterium fissicatena group (q ≤ 0.007), while the IF2-P group had a significant increase in abundance of Ruminococcaceae Incertae Sedis and a decrease in Eubacterium ventriosum group (q ≤ 0.005). The plasma metabolite profile of IF2-P participants displayed significant increases in serine, trimethylamine oxide (TMAO), levulinic acid, 3-aminobutyric acid, citrate, isocitrate, and glucuronic acid (q ≤ 0.049) compared to IF1-P. Fecal short-chain fatty acid concentrations did not differ significantly by time or between groups (p ≥ 0.126). Interestingly, gastrointestinal symptoms were significantly reduced for the IF2-P group but not for the IF1-P group. Our results demonstrate that short-term IF modestly influenced the GM community structure and the plasma metabolome, suggesting these protocols could be viable for certain nutritional intervention strategies.

Global patterns in symbiont selection and transmission strategies in sponges

Sponges host dense and diverse communities of microbes (known as the microbiome) beneficial for the host nutrition and defense. Symbionts in turn receive shelter and metabolites from the sponge host, making their relationship beneficial for both partners. Given that sponge-microbes associations are fundamental for the survival of both, especially the sponge, such relationship is maintained through their life and even passed on to the future generations. In many organisms, the microbiome has profound effects on the development of the host, but the influence of the microbiome on the reproductive and developmental pathways of the sponges are less understood. In sponges, microbes are passed on to oocytes, sperm, embryos, and larvae (known as vertical transmission), using a variety of methods that include direct uptake from the mesohyl through phagocytosis by oocytes to indirect transmission to the oocyte by nurse cells. Such microbes can remain in the reproductive elements untouched, for transfer to offspring, or can be digested to make the yolky nutrient reserves of oocytes and larvae. When and how those decisions are made are fundamentally unanswered questions in sponge reproduction. Here we review the diversity of vertical transmission modes existent in the entire phylum Porifera through detailed imaging using electron microscopy, available metabarcoding data from reproductive elements, and macroevolutionary patterns associated to phylogenetic constraints. Additionally, we examine the fidelity of this vertical transmission and possible reasons for the observed variability in some developmental stages. Our current understanding in marine sponges, however, is that the adult microbial community is established by a combination of both vertical and horizontal (acquisition from the surrounding environment in each new generation) transmission processes, although the extent in which each mode shapes the adult microbiome still remains to be determined. We also assessed the fundamental role of filtration, the cellular structures for acquiring external microbes, and the role of the host immune system, that ultimately shapes the stable communities of prokaryotes observed in adult sponges.

Xanthohumol microbiome and signature in adults with Crohn’s disease (the XMaS trial): a protocol for a phase II triple-masked, placebo-controlled clinical trial

BackgroundXanthohumol (XN), a bioactive flavonoid from Humulus lupulus with anti-inflammatory properties, has potential benefits for patients with Crohn’s disease (CD), a type of inflammatory bowel disease. We recently completed and published results of a placebo-controlled phase I clinical trial demonstrating the safety and tolerability of 24 mg XN daily for 8 weeks. The present study aims to evaluate the safety and tolerability of the same dose of XN adults with clinically active CD in a placebo-controlled phase II clinical trial. Additional aims will assess the impact of XN on inflammatory biomarkers, platelet function, CD clinical activity, and stool microbial composition. The metabolism of XN will also be evaluated. This article provides a model protocol for consideration in investigations of XN or other natural products in disease states.MethodsA triple-masked, randomized, placebo-controlled trial will be conducted in adults with clinically active CD. Participants (n ≤ 32) will be randomized to either 24 mg encapsulated XN per day or placebo and followed for 8 weeks. Throughout the trial, participants will be queried for adverse events. Biomarkers of clinical safety, blood and stool markers of inflammation, platelet function, Crohn’s Disease Activity Index score, stool microbial composition, and XN metabolite profiles in blood, urine, and stool will be assessed every 2 weeks.DiscussionWe describe the protocol for a phase II clinical trial that evaluates the safety and tolerability of XN in adults with active CD, as well as evaluate metabolism and mechanisms that are relevant to CD and other diseases with underlying inflammation and/or gut permeability. The effects of XN on inflammatory biomarkers, platelet function, the microbiota, and multi-omics biomarkers measured in this phase II trial of adults with CD will be compared to the effects of XN in healthy adults in our previous phase I trial. The results of the study will advance the evidence guiding the use of XN in patients with CD.Trial registrationClinialTrials.gov NCT04590508. Registered on October 19, 2020

Characterization of the Intestinal Microbiome in Healthy Adults over Sars-Cov-2 Vaccination.

In response to the outbreak of coronavirus disease 2019 (COVID-19) worldwide, inactivated severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines are implemented. Dysbiosic gut microbiota is implicated in the COVID-19 patients. Whereas, how intestinal microbiota are affected by vaccination remains elusive, and it is important to investigate the microbial shifts during vaccines treatment. In the present study, we assessed the gut microbial composition in healthy adults, and performed comparison before and post an inactivated SARS-CoV-2 vaccine candidate, BBIBP-CorV vaccination. Microbial diversity in shannon, pielou evenness, simpson and invsimpson index was remarkably suppressed by vaccination. Ruminococcus and Actinomyces were observed to be strikingly deficient, and Faecalibacterium was dramatically augmented after BBIBP-CorV treatment. Potential functional profiles of gut microbiome in amino acid metabolism, lipid biosynthesis proteins and steroid biosynthesis were remarkably increased, while the capacity in renin-angiotensin system was remarkably decreased following vaccines. Our study suggests that inactivated BBIBP-CorV against SARS-CoV-2 could elicit modulations on gut microbial composition and functions, which might favor host immune response and protect from COVID-19.

Ribosomal RNA-Depletion Provides an Efficient Method for Successful Dual RNA-Seq Expression Profiling of a Marine Sponge Holobiont

Investigations of host-symbiont interactions can benefit enormously from a complete and reliable holobiont gene expression profiling. The most efficient way to acquire holobiont transcriptomes is to perform RNA-Seq on both host and symbionts simultaneously. However, optimal methods for capturing both host and symbiont mRNAs are still under development, particularly when the host is a eukaryote and the symbionts are bacteria or archaea. Traditionally, poly(A)-enriched libraries have been used to capture eukaryotic mRNA, but the ability of this method to adequately capture bacterial mRNAs is unclear because of the short half-life of the bacterial transcripts. Here, we address this gap in knowledge with the aim of helping others to choose an appropriate RNA-Seq approach for analysis of animal host-bacterial symbiont transcriptomes. Specifically, we compared transcriptome bias, depth and coverage achieved by two different mRNA capture and sequencing strategies applied to the marine demosponge Amphimedon queenslandica holobiont. Annotated genomes of the sponge host and the three most abundant bacterial symbionts, which can comprise up to 95% of the adult microbiome, are available. Importantly, this allows for transcriptomes to be accurately mapped to these genomes, and thus quantitatively assessed and compared. The two strategies that we compare here are (i) poly(A) captured mRNA-Seq (Poly(A)-RNA-Seq) and (ii) ribosomal RNA depleted RNA-Seq (rRNA-depleted-RNA-Seq). For the host sponge, we find no significant difference in transcriptomes generated by the two different mRNA capture methods. However, for the symbiont transcriptomes, we confirm the expectation that the rRNA-depleted-RNA-Seq performs much better than the Poly(A)-RNA-Seq. This comparison demonstrates that RNA-Seq by ribosomal RNA depletion is an effective and reliable method to simultaneously capture gene expression in host and symbionts and thus to analyse holobiont transcriptomes.

Alterations in the Oral Microbiome Associated With Diabetes, Overweight, and Dietary Components.

The Mediterranean diet (MedDiet) represents the traditional food consumption patterns of people living in countries bordering the Mediterranean Sea and is associated with a reduced incidence of obesity and type-2 diabetes mellitus (T2DM). The objective of this study was to examine differences in the composition of the oral microbiome in older adults with T2DM and/or high body mass index (BMI) and whether the microbiome was influenced by elements of a MedDiet. Using a nested case-control design individuals affected by T2DM were selected from the Seniors-ENRICA-2 cohort concurrently with non-diabetic controls. BMI was measured, a validated dietary history taken, and adherence to a Mediterranean diet calculated using the MEDAS (Mediterranean Diet Adherence Screener) index. Oral health status was assessed by questionnaire and unstimulated whole mouth saliva was collected, and salivary flow rate calculated. Richness and diversity of the salivary microbiome were reduced in participants with T2DM compared to those without diabetes. The bacterial community structure in saliva showed distinct “signatures” or “salivatypes,” characterized by predominance of particular bacterial genera. Salivatype 1 was more represented in subjects with T2DM, whilst those with obesity (BMI ≥ 30 kg/m2) had a predominance of salivatype 2, and control participants without T2DM or obesity had an increased presence of salivatype 3. There was an association of salivatype 1 with increased consumption of sugary snacks combined with reduced consumption of fish/shellfish and nuts. It can be concluded that the microbial community structure of saliva is altered in T2DM and obesity and is associated with altered consumption of particular food items. In order to further substantiate these observations a prospective study should be undertaken to assess the impact of diets aimed at modifying diabetic status and reducing weight.

Effects of Human Milk Oligosaccharides on Microbiome

Human Milk Oligosaccharides (HMOs), the complex, unique glycans present in human milk, are essential for infants’ early development and provide many health benefits to humans. Although the effects of all the individual HMOs are not fully understood, studies have revealed many health benefits of HMOs acting as prebiotics. They shape the gut microbiome, provide immune-modulatory and anti-adhesive effects to enhance innate and acquired immunity in the host and modulate the epithelial barrier. The effects of HMOs are not only limited to the infant gut microbiome but also affect the microbiome of breast milk and adults. This mini review highlights the recent findings on the effects of HMOs on the microbiome. It discusses the benefit of synthesizing and identifying the structures of individual glycans for further improvement in human health.

Supplementation of a single species probiotic does not affect diversity and composition of the healthy adult gastrointestinal microbiome

Over several years, consumer probiotic consumption has increased substantially. Consequently, the number of over-the-counter probiotic products available to consumers has also increased. Many consumers use probiotics for preventative purposes rather than to treat specific illnesses. The influence of probiotics on the healthy human gut microbiome has not been extensively studied and many questions remain regarding the influence of probiotic supplementation on existing gut flora. In this study, the effect of a commercial probiotic containing Bifidobacterium infantis on the composition and diversity of gut flora in healthy adults was examined. Thirty participants were enrolled in the study and randomly assigned to probiotic (n = 15) or placebo (n = 15) groups. Over the course of the study, three stool samples were collected to facilitate baseline, probiotic/placebo effect, and return to baseline measurements. The probiotic/placebo effect samples were collected after taking a probiotic/placebo tablet daily for 30 days, and the return to baseline sample was collected 30 days after completing the treatment course. V3/V4 16S rRNA sequencing was performed on all samples and data was analyzed using QIIME. No significant difference in gut community diversity or composition between probiotic and placebo groups was observed. This finding suggests that use of a single species probiotic in healthy individuals does not significantly influence microbial gastrointestinal diversity.

Dosing a synbiotic of human milk oligosaccharides and B. infantis leads to reversible engraftment in healthy adult microbiomes without antibiotics

Predictable and sustainable engraftment of live biotherapeutic products into the human gut microbiome is being explored as a promising way to modulate the human gut microbiome. We utilize a synbiotic approach pairing the infant gut microbe Bifidobacterium longum subspecies infantis (B.infantis) and human milk oligosaccharides (HMO). B. infantis, which is typically absent in adults, engrafts into healthy adult microbiomes in an HMO-dependent manner at a relative abundance of up to 25% of the bacterial population without antibiotic pretreatment or adverse effects. Corresponding changes in metabolites are detected. Germ-free mice transplanted with dysbiotic human microbiomes also successfully engraft with B.infantis in an HMO-dependent manner, and the synbiotic augments butyrate levels both in this invivo model and in invitro coculturesof the synbiotic with specific Firmicutes species. Finally, the synbiotic inhibits the growth of enteropathogensinvitro. Our findings point to a potential safe mechanism for ameliorating dysbioses characteristicof numerous human diseases.

The Pandemic Effects on the Microbiome of Infants in the Neonatal Intensive Care Unit (NICU)

The microbiome is an *invisible organ* that affects health and disease. Early life microbial colonization is critical for development of the immune system, postnatal growth, and long‐term health. The dynamic and nascent microbiomes of children are highly individualized. SARS‐CoV‐2(Covid‐19) is known to impact the adult microbiome. However, pandemic impact on the infant microbiome is unknown. In the current study we hypothesized that infants born prior to pandemic regulations may demonstrate differences compared to those born during the pandemic. Fecal samples (n=307) were collected from infants (1‐19 weeks) in the NICU at The University of Chicago. DNA was extracted for 16S rRNA sequencing, and 4576 taxa were analyzed using R. We performed alpha diversity analysis within the samples and beta diversity between the samples to measure and compare bacterial communities. Alpha diversity did not demonstrate a significant difference between before pandemic and during pandemic groups, while Beta diversity did achieve a significant difference between the two groups. Multivariate analysis showed that in before pandemic and during pandemic groups, post menstrual age (PMA), weeks of life (WOL), as well as the interactions of pandemic grouping by PMA, and PMA by WOL were significant. Lastly, we identified the top 5 positively associated and top 5 negatively associated bacteria at the species/genus level associated with the pandemic grouping. Of these, Serratia marcescens and Acinetobacter johnsonii are associated with antibiotic resistance, and reduction of human pathogens such as Shigellaand Salmonella.This study illustrates that differences in microbiome diversity exist between infants before and after pandemic regulations. Any disruptions in microbial colonization can contribute to shifts in normal microbial colonization that persist past the first 1000 days of life. Our study suggests the possible influences of secondary factors during the pandemic on microbiome development. In future studies we plan to further explore the interaction of cofounders (e.g. PMA) as well as follow up on the long‐term effects of the pandemic on the infant microbiome.

Oral Microbiome of Adults in Sound and Cariogenic Biofilm with and without Dental Caries. A Pilot Study

Oral Microbiome of Adults in Sound and Cariogenic Biofilm with and without Dental Caries. A Pilot Study

Characterising the tear bacterial microbiome in young adults

Conjunctival swabs (CS) are the major source of sampling for ocular microbiome studies, however collecting CS from the diseased eyes is difficult and painful. In this study, as an alternative to CS, a less invasive approach of tear collection was used to establish the bacterial microbiome in healthy eyes. Tear bacterial microbiome was generated from the DNA of tears (n = 24; male = 16 and female = 8) of healthy volunteers aged from 20 to 52 years. Sequencing of V3–V4 region of 16S rRNA gene was performed on the Illumina platform. Reads were processed in QIIME to assign the taxa. Statistical analysis of the tear microbiome was done in R to assess the alphadiversity and betadiversity indices. Tear microbiome was generated in all the 24 tear samples. Eight out of the top 10 predominant bacterial genera remained same in both tear and CS microbiomes, which include genera such as Corynebacterium, Staphylococcus, Streptococcus, Mycobacterium, Escherichia-Shigella, Lactobacillus, Bacillus and Acinetobacter. The similarity network analysis indicates that 144 out of 145 genera of tear cohort matched with conjunctival swabs. However, tear and CS microbiomes differed in the abundance of the predominant bacterial genera. The bacterial microbiome of tears in adults appears to be stable and is comparable with that of CS microbiome.

Distinct Serum and Fecal Metabolite Profiles Linking With Gut Microbiome in Older Adults With Frailty.

Frailty is a critical aging-related syndrome but the underlying metabolic mechanism remains poorly understood. The aim of this study was to identify novel biomarkers and reveal potential mechanisms of frailty based on the integrated analysis of metabolome and gut microbiome. In this study, twenty subjects consisted of five middle-aged adults and fifteen older adults, of which fifteen older subjects were divided into three groups: non-frail, pre-frail, and frail, with five subjects in each group. The presence of frailty, pre-frailty, or non-frailty was established according to the physical frailty phenotype (PFP). We applied non-targeted metabolomics to serum and feces samples and used 16S rDNA gene sequencing to detect the fecal microbiome. The associations between metabolites and gut microbiota were analyzed by the Spearman’s correlation analysis. Serum metabolic shifts in frailty mainly included fatty acids and derivatives, carbohydrates, and monosaccharides. Most of the metabolites belonging to these classes increased in the serum of frail older adults. Propylparaben was found to gradually decrease in non-frail, pre-frail, and frail older adults. Distinct changes in fecal metabolite profiles and gut microbiota were also found among middle-aged adults, non-frail and frail older subjects. The relative abundance of Faecalibacteriu, Roseburia, and Fusicatenibacter decreased while the abundance of Parabacteroides and Bacteroides increased in frailty. The above altered microbes were associated with the changed serum metabolites in frailty, which included dodecanedioic acid, D-ribose, D-(-)-mannitol, creatine and indole, and their related fecal metabolites. The changed microbiome and related metabolites may be used as the biomarkers of frailty and is worthy of further mechanistic studies.

Acute and persistent effects of commonly used antibiotics on the gut microbiome and resistome in healthy adults.

SUMMARYAntibiotics are deployed against bacterial pathogens, but their targeting of conserved microbial processes means they also collaterally perturb the commensal microbiome. To understand acute and persistent effects of antibiotics on the gut microbiota of healthy adult volunteers, we quantify microbiome dynamics before, during, and 6 months after exposure to 4 commonly used antibiotic regimens. We observe an acute decrease in species richness and culturable bacteria after antibiotics, with most healthy adult microbiomes returning to pre-treatment species richness after 2 months, but with an altered taxonomy, resistome, and metabolic output, as well as an increased antibiotic resistance burden. Azithromycin delays the recovery of species richness, resulting in greater compositional distance. A subset of volunteers experience a persistent reduction in microbiome diversity after antibiotics and share compositional similarities with patients hospitalized in intensive care units. These results improve our quantitative understanding of the impact of antibiotics on commensal microbiome dynamics, resilience, and recovery.

Metagenomic strain detection with SameStr: identification of a persisting core gut microbiota transferable by fecal transplantation

BackgroundThe understanding of how microbiomes assemble, function, and evolve requires metagenomic tools that can resolve microbiota compositions at the strain level. However, the identification and tracking of microbial strains in fecal metagenomes is challenging and available tools variably classify subspecies lineages, which affects their applicability to infer microbial persistence and transfer.ResultsWe introduce SameStr, a bioinformatic tool that identifies shared strains in metagenomes by determining single-nucleotide variants (SNV) in species-specific marker genes, which are compared based on a maximum variant profile similarity. We validated SameStr on mock strain populations, available human fecal metagenomes from healthy individuals and newly generated data from recurrent Clostridioides difficile infection (rCDI) patients treated with fecal microbiota transplantation (FMT). SameStr demonstrated enhanced sensitivity to detect shared dominant and subdominant strains in related samples (where strain persistence or transfer would be expected) when compared to other tools, while being robust against false-positive shared strain calls between unrelated samples (where neither strain persistence nor transfer would be expected). We applied SameStr to identify strains that are stably maintained in fecal microbiomes of healthy adults over time (strain persistence) and that successfully engraft in rCDI patients after FMT (strain engraftment). Taxonomy-dependent strain persistence and engraftment frequencies were positively correlated, indicating that a specific core microbiota of intestinal species is adapted to be competitive both in healthy microbiomes and during post-FMT microbiome assembly. We explored other use cases for strain-level microbiota profiling, as a metagenomics quality control measure and to identify individuals based on the persisting core gut microbiota.ConclusionSameStr provides for a robust identification of shared strains in metagenomic sequence data with sufficient specificity and sensitivity to examine strain persistence, transfer, and engraftment in human fecal microbiomes. Our findings identify a persisting healthy adult core gut microbiota, which should be further studied to shed light on microbiota contributions to chronic diseases.Bmxg3NA25n3myfWhCsfsJVVideo abstract

Modulatory Effects of Huoxiang Zhengqi Oral Liquid on Gut Microbiome Homeostasis Based on Healthy Adults and Antibiotic-Induced Gut Microbial Dysbiosis Mice Model.

Traditional herbal medicine (THM) is used worldwide for its safety and effectiveness against various diseases. Huoxiang Zhengqi (HXZQ) is an extensively used Chinese THM formula targeting gastrointestinal disordered gastroenteritis via regulating the intestinal microbiome/immuno-microenvironment. However, the specific mechanisms remain largely unexplored, besides as a lifestyle drug, its safety on the gut microbiome homeostasis has never been investigated. In this study, the effects of HXZQ on the gut microbiome of healthy adults were investigated for the first time, and the antibiotic-induced gut microbiota dysbiosis mice model was applied for verification. Based on healthy adults, our results revealed that HXZQ exhibited mild and positive impacts on the bacterial diversity and the composition of the gut microbiome in a healthy state. As for an unhealthy state of the gut microbiome (with low bacterial diversity and deficient compositions), HXZQ significantly restored the bacterial diversity and recovered the abundance of Bacteroidetes. In the antibiotic-induced mice model, HXZQ distinctly revived the deficient gut microbial compositions impaired by antibiotics. At the genus level, the abundances that responded most strongly and positively to HXZQ were Bifidobacterium in healthy adults and Muribaculaceae, Lactobacillus, and Akkermansia in mice. In contrast, the abundance of Blautia in healthy adults, Enterococcus, and Klebsiella in mice showed inversely associated with HXZQ administration. At last, HXZQ might exhibit an anti-inflammatory effect by regulating the concentration of interleukin-6 in plasma while causing no significant changes in the colon tissue structure in mice. In conclusion, our results elucidate that the safety of HXZQ in daily use further reveals the modulatory effects of HXZQ on gut microbial community structure. These results will provide new insights into the interaction of THM and gut microbiome homeostasis and clues about the safe use of THM as a lifestyle drug for its further development.

Identifying biomarkers of the gut bacteria, bacteriophages and serum metabolites associated with three weaning periods in piglets

BackgroundThe establishment of the piglet gut microbiome has a prolonged influence on host health, as it sets the stage for establishment of the adult swine microbiome. Substantial changes in host metabolism and immunity around the time of weaning may be accompanied by alterations in the gut microbiome. In this study, we systematically evaluated differences in the gut microbiome and host metabolites among three weaning periods using shotgun metagenomic sequencing and untargeted metabolomic profiling in piglets.ResultsWe identified that P. copri was the most significantly different species among three weaning periods, and was the key bacterial species for mitigating piglet adaptation during the weaning transition, while Bacillus_phage_BCD7, the only differential bacteriophages, was significantly and positively correlated with P. copri enriched in day 28 group. Additionally, P. copri and Bacillus_phage_BCD7 was significantly correlated with the shifts of functional capacities of the gut microbiome and several CAZymes in day 28 group. Furthermore, the altered metabolites we observed were enriched in pathways matched to the functional capacity of the gut microbiome e.g., aminoacyl-tRNA biosynthesis.ConclusionThe results from this study indicate that the bacteria-phage interactions and host-microbial interactions during the weaning transition impact host metabolism, leading to beneficial host changes among three weaning periods.