Dynamics Of Gut Microbiome Research Articles

Longitudinal analysis reveals transition barriers between dominant ecological states in the gut microbiome

The Pioneer 100 Wellness Project involved quantitatively profiling 108 participants' molecular physiology over time, including genomes, gut microbiomes, blood metabolomes, blood proteomes, clinical chemistries, and data from wearable devices. Here, we present a longitudinal analysis focused specifically around the Pioneer 100 gut microbiomes. We distinguished a subpopulation of individuals with reduced gut diversity, elevated relative abundance of the genus Prevotella, and reduced levels of the genus Bacteroides We found that the relative abundances of Bacteroides and Prevotella were significantly correlated with certain serum metabolites, including omega-6 fatty acids. Primary dimensions in distance-based redundancy analysis of clinical chemistries explained 18.5% of the variance in bacterial community composition, and revealed a Bacteroides/Prevotella dichotomy aligned with inflammation and dietary markers. Finally, longitudinal analysis of gut microbiome dynamics within individuals showed that direct transitions between Bacteroides-dominated and Prevotella-dominated communities were rare, suggesting the presence of a barrier between these states. One implication is that interventions seeking to transition between Bacteroides- and Prevotella-dominated communities will need to identify permissible paths through ecological state-space that circumvent this apparent barrier.

Intestinal microbiota domination under extreme selective pressures characterized by metagenomic read cloud sequencing and assembly

BackgroundLow diversity of the gut microbiome, often progressing to the point of intestinal domination by a single species, has been linked to poor outcomes in patients undergoing hematopoietic cell transplantation (HCT). Our ability to understand how certain organisms attain intestinal domination over others has been restricted in part by current metagenomic sequencing technologies that are typically unable to reconstruct complete genomes for individual organisms present within a sequenced microbial community. We recently developed a metagenomic read cloud sequencing and assembly approach that generates improved draft genomes for individual organisms compared to conventional short-read sequencing and assembly methods. Herein, we applied metagenomic read cloud sequencing to four stool samples collected longitudinally from an HCT patient preceding treatment and over the course of heavy antibiotic exposure.ResultsCharacterization of microbiome composition by taxonomic classification of reads reveals that that upon antibiotic exposure, the subject’s gut microbiome experienced a marked decrease in diversity and became dominated by Escherichia coli. While diversity is restored at the final time point, this occurs without recovery of the original species and strain-level composition. Draft genomes for individual organisms within each sample were generated using both read cloud and conventional assembly. Read clouds were found to improve the completeness and contiguity of genome assemblies compared to conventional assembly. Moreover, read clouds enabled the placement of antibiotic resistance genes present in multiple copies both within a single draft genome and across multiple organisms. The occurrence of resistance genes associates with the timing of antibiotics administered to the patient, and comparative genomic analysis of the various intestinal E. coli strains across time points as well as the bloodstream isolate showed that the subject’s E. coli bloodstream infection likely originated from the intestine. The E. coli genome from the initial pre-transplant stool sample harbors 46 known antimicrobial resistance genes, while all other species from the pre-transplant sample each contain at most 5 genes, consistent with a model of heavy antibiotic exposure resulting in selective outgrowth of the highly antibiotic-resistant E. coli.ConclusionThis study demonstrates the application and utility of metagenomic read cloud sequencing and assembly to study the underlying strain-level genomic factors influencing gut microbiome dynamics under extreme selective pressures in the clinical context of HCT.

Persistent Gut Microbial Dysbiosis in Children with Acute Lymphoblastic Leukemia (ALL) During Chemotherapy.

Prophylactic or therapeutic antibiotic use along with chemotherapy treatment potentially has a long-standing adverse effect on the resident gut microbiota. We have established a case-control cohort of 32 pediatric and adolescent acute lymphoblastic leukemia (ALL) patients and 25 healthy siblings (sibling controls) to assess the effect of chemotherapy as well as antibiotic prophylaxis on the gut microbiota. We observe that the microbiota diversity and richness of the ALL group is significantly lower than that of the control group at diagnosis and during chemotherapy. The microbiota diversity is even lower in antibiotics-exposed ALL patients. Although the gut microbial diversity tends to stabilize after 1-year post-chemotherapy, their abundances were altered because of chemotherapy and prophylactic antibiotic treatments. Specifically, the abundances of mucolytic gram-positive anaerobic bacteria, including Ruminococcus gnavus and Ruminococcus torques, tended to increase during the chemotherapy regimen and continued to be elevated 1 year beyond the initiation of chemotherapy. This dysbiosis may contribute to the development of gastrointestinal complications in ALL children following chemotherapy. These findings set the stage to further understand the role of the gut microbiome dynamics in ALL patients and their potential role in alleviating some of the adverse side effects of chemotherapy and antibiotics use in immunocompromised children.

Gut Microbiome in Psoriasis is Perturbed Differently During Secukinumab and Ustekinumab Therapy and Associated with Response to Treatment.

Immunotherapy could change the complex host-microbial interactions. We aimed to investigate the dynamics of gut microbiome in response to secukinumab [an interleukin (IL)-17 inhibitor] and ustekinumab (an IL-12/23 inhibitor) therapy and its association with treatment response in psoriasis. This observational, longitudinal study collected a total of 114 fecal samples from 12 healthy controls and 34 patients with psoriasis at baseline and 3 and 6months after secukinumab (n = 24) or ustekinumab treatment (n = 10) and gut microbiomes were investigated using next-generation sequencing targeting 16S ribosomal RNA. Secukinumab treatment causes more profound alterations in gut microbiome, including increases in the relative abundance of phylum Proteobacteria and decreases in Bacteroidetes and Firmicutes, than ustekinumab treatment. The relative abundance of family Pseudomonadaceae, family Enterobacteriaceae and order Pseudomonadales also increased significantly following secukinumab therapy. In contrast, there was no significant change in gut microbiome composition following ustekinumab treatment, and only genus Coprococcus significantly increased after 6months of ustekinumab therapy. Moreover, we observed significant differences in baseline gut microbiome between responders and non-responders to secukinumab treatment. These results indicate that gut microbiome is altered differently after anti-IL17 and anti-IL12/23 treatment. Secukinumab (anti-IL17) therapy is associated with distinct and more profound gut microbiome shifts than ustekinumab therapy (anti-IL 12/23) in patients with psoriasis. Moreover, gut microbiome would serve as potential biomarkers of response to secukinumab treatment.

Primate microbiomes over time: Longitudinal answers to standing questions in microbiome research.

To date, most insights into the processes shaping vertebrate gut microbiomes have emerged from studies with cross-sectional designs. While this approach has been valuable, emerging time series analyses on vertebrate gut microbiomes show that gut microbial composition can change rapidly from 1 day to the next, with consequences for host physical functioning, health, and fitness. Hence, the next frontier of microbiome research will require longitudinal perspectives. Here we argue that primatologists, with their traditional focus on tracking the lives of individual animals and familiarity with longitudinal fecal sampling, are well positioned to conduct research at the forefront of gut microbiome dynamics. We begin by reviewing some of the most important ecological processes governing microbiome change over time, and briefly summarizing statistical challenges and approaches to microbiome time series analysis. We then introduce five questions of general interest to microbiome science where we think field-based primate studies are especially well positioned to fill major gaps: (a) Do early life events shape gut microbiome composition in adulthood? (b) Do shifting social landscapes cause gut microbial change? (c) Are gut microbiome phenotypes heritable across variable environments? (d) Does the gut microbiome show signs of host aging? And (e) do gut microbiome composition and dynamics predict host health and fitness? For all of these questions, we highlight areas where primatologists are uniquely positioned to make substantial contributions. We review preliminary evidence, discuss possible study designs, and suggest future directions.

Gut Microbiota Dysbiosis and Their Impact on Biochemical and Inflammatory Profiles in Cafeteria Diet Fed Sprague Dawley Rats

Gut microbiota plays a major role in regulating the host metabolism and immune system. However, the structure of microbiome population is altered constantly by diverse factors including diet and environment. In particular, the gut microbiome dynamics is influenced by diet composition and their associated metabolites. Many studies in the recent past reported on diet induced dysbiosis in the gut microbiome, the modulating ratio between Firmicutes and Bacteroidetes plays a central role in maintaining the microbiome diversity in the gut and their abundance regulates obese conditions. Although there are several reports on gut microbial dysbiosis (Firmicutes/Bacteroidetes) at phylum level but only few of them highlight at the genera level. In the present study, we focused more on the impact of cafeteria diet (CAF) with respect to the gut microbiome richness at the genera level in SD rats. Three weeks old Sprague Dawley (SD) rats were fed with normal chow diet and cafeteria diet (CAF). After 10 weeks, serum, tissue samples (small intestine and cecum), cecum fecal and fecal pellet were collected. Biochemical analysis from serum, Gene expression analysis of pro-inflammatory markers from tissues and microbiome analysis from fecal samples were analysed. CAF diet fed rat in the present study developed obesity with increased body weight, few of them developed the resistance to weight gain (WGR) and these animal shows significantly increased abundance of Bacteriodetes-Prevotella compared to obese animals. This study suggests that detailed research needed to address the contribution of microbiota abundance at the genera level. We further explored the influence of diet induced microbiota changes on immune response; increase in Bacteroidetes leads to increased LPS and this in turn elicit immune reaction in the gut. Moreover, variation in gut microbiota also affects the gut barrier function (Tight junction proteins) and increase metabolic endotoxemia that leads to activation of innate immune system and low-grade inflammation. Further studies on these lines targeting the microbiota changes in the gut at the genera level is warranted to gain more knowledge.

Dynamics of Gut Microbiome in Giant Panda Cubs Reveal Transitional Microbes and Pathways in Early Life.

Adult giant pandas (Ailuropoda melanoleuca) express transitional characteristics in that they consume bamboos, despite their carnivore-like digestive tracts. Their genome contains no cellulolytic enzymes; therefore, understanding the development of the giant panda gut microbiome, especially in early life, is important for decoding the rules underlying gut microbial formation, inheritance and dietary transitions. With deep metagenomic sequencing, we investigated the gut microbiomes of two newborn giant panda brothers and their parents living in Macao, China, from 2016 to 2017. Both giant panda cubs exhibited progressive increases in gut microbial richness during growth, particularly from the 6th month after birth. Enterobacteriaceae dominated the gut microbial compositions in both adult giant pandas and cubs. A total of 583 co-abundance genes (CAGs) and about 79 metagenomic species (MGS) from bacteria or viruses displayed significant changes with age. Seven genera (Shewanella, Oblitimonas, Helicobacter, Haemophilus, Aeromonas, Listeria, and Fusobacterium) showed great importance with respect to gut microbial structural determination in the nursing stage of giant panda cubs. Furthermore, 10 orthologous gene functions and 44 pathways showed significant changes with age. Of the significant pathways, 16 from Escherichia, Klebsiella, Propionibacterium, Lactobacillus, and Lactococcus displayed marked differences between parents and their cubs at birth, while 29 pathways from Escherichia, Campylobacter and Lactobacillus exhibited significant increase in cubs from 6 to 9 months of age. In addition, oxidoreductases, transferases, and hydrolases dominated the significantly changed gut microbial enzymes during the growth of giant panda cubs, while few of them were involved in cellulose degradation. The findings indicated diet-stimulated gut microbiome transitions and the important role of Enterobacteriaceae in the guts of giant panda in early life.

Biotic and abiotic factors influencing channel catfish egg and gut microbiome dynamics during early life stages

This study quantified the effects of pond rearing environments on microbial community composition in larval channel catfish (Ictalurus punctatus) gastrointestinal (GI) tracts across early developmental stages. Larvae were reared under standard industry conditions and sampled at five developmental stages (Egg, Swim-up, Day of stocking, 24 h post-stocking, and 21 d post-stocking). Massive-parallel sequencing of a segment of the 16S rRNA gene was conducted using an Illumina MiSeq platform to characterize the diversity and taxonomic composition of gut and water microbial communities. PERMANOVA analyses of differences in egg and gut microbial community composition across stages indicated a significant interaction between nursery pond environment, and family (P < 0.05) during the last two stages. Proteobacteria and Firmicutes genera along with genera including Vibrio, Aeromonas and Flavobacterium were associated with differences in gut bacterial community composition during larval development before and after pond stocking. Our study demonstrates that the aquatic rearing environment is an important factor influencing the transfer of microbes from water or food into the gut, and provides insight concerning the niche and ecological adaptability of microbes inside the channel catfish gut. Findings demonstrating that catfish gut community composition is highly variable over time indicates probiotic treatments may be possible, however gut community manipulation would require concurrent manipulation of pond or other environmental regimes and microbial communities.

\u2018Cyclical Bias\u2019 in Microbiome Research\xa0Revealed by\xa0A Portable Germ-Free Housing System Using\xa0Nested Isolation

Germ-Free (GF) research has required highly technical pressurized HEPA-ventilation anchored systems for decades. Herein, we validated a GF system that can be easily implemented and portable using Nested Isolation (NesTiso). GF-standards can be achieved housing mice in non-HEPA-static cages, which only need to be nested ‘one-cage-inside-another’ resembling ‘Russian dolls’. After 2 years of monitoring ~100,000 GF-mouse-days, NesTiso showed mice can be maintained GF for life (>1.3 years), with low animal daily-contamination-probability risk (1 every 867 days), allowing the expansion of GF research with unprecedented freedom and mobility. At the cage level, with 23,360 GF cage-days, the probability of having a cage contamination in NesTiso cages opened in biosafety hoods was statistically identical to that of opening cages inside (the ‘gold standard’) multi-cage pressurized GF isolators. When validating the benefits of using NesTiso in mouse microbiome research, our experiments unexpectedly revealed that the mouse fecal microbiota composition within the ‘bedding material’ of conventional SPF-cages suffers cyclical selection bias as moist/feces/diet/organic content (‘soiledness’) increases over time (e.g., favoring microbiome abundances of Bacillales, Burkholderiales, Pseudomonadales; and cultivable Enterococcus faecalis over Lactobacillus murinus and Escherichia coli), which in turn cyclically influences the gut microbiome dynamics of caged mice. Culture ‘co-streaking’ assays showed that cohoused mice exhibiting different fecal microbiota/hemolytic profiles in clean bedding (high-within-cage individual diversity) ‘cyclically and transiently appear identical’ (less diverse) as bedding soiledness increases, and recurs. Strategies are proposed to minimize this novel functional form of cyclical bedding-dependent microbiome selection bias.

The impact of pollen consumption on honey bee (Apis mellifera) digestive physiology and carbohydrate metabolism.

Carbohydrate-active enzymes play an important role in the honey bee (Apis mellifera) due to its dietary specialization on plant-based nutrition. Secretory glycoside hydrolases (GHs) produced in worker head glands aid in the processing of floral nectar into honey and are expressed in accordance with age-based division of labor. Pollen utilization by the honey bee has been investigated in considerable detail, but little is known about the metabolic fate of indigestible carbohydrates and glycosides in pollen biomass. Here, we demonstrate that pollen consumption stimulates the hydrolysis of sugars that are toxic to the bee (xylose, arabinose, mannose). GHs produced in the head accumulate in the midgut and persist in the hindgut that harbors a core microbial community composed of approximately 108 bacterial cells. Pollen consumption significantly impacted total and specific bacterial abundance in the digestive tract. Bacterial isolates representing major fermentative gut phylotypes exhibited primarily membrane-bound GH activities that may function in tandem with soluble host enzymes retained in the hindgut. Additionally, we found that plant-originating β-galactosidase activity in pollen may be sufficient, in some cases, for probable physiological activity in the gut. These findings emphasize the potential relative contributions of host, bacteria, and pollen enzyme activities to carbohydrate breakdown, which may be tied to gut microbiome dynamics and associated host nutrition.

Characterization of Gut Microbiome Dynamics in Developing Pekin Ducks and Impact of Management System.

Little to no research has been conducted on the gut microbiome of the Pekin duck, yet over 24.5 million ducks are raised for human consumption each year in the United States alone. Knowledge of the microbiome could lead to an understanding of the effects of growing conditions such as the use of prebiotics, probiotics, and enzymes in feeding practices, the use of antibiotics, and the sources of pathogenic bacteria in diseased ducks. In order to characterize changes in the caecal microbiome that occur as ducks develop through a typical industry grow-out period, a 16S rRNA community analysis of caecal contents collected over a 6-week period was conducted using a next generation sequencing approach. Transitions in the composition of the caecal microbiome occurred throughout the lifespan, with a large shift during days 4 through 10 posthatch. Two major phyla of bacteria were found to be present within the caeca of aviary raised ducks, with the relative abundance of each phylum varying by age of the duck. Proteobacteria is dominant for the first 3 days of age, and Firmicutes increases and dominates beginning at day 4. Barn raised ducks contained a significant population of Bacteroidetes in addition to Proteobacteria and Firmicutes at later developmental time points, though this phylum was absent in aviary raised ducks. Genera containing pathogens of anseriformes most often found in industry settings were either absent or found as normal parts of the caecal microbial populations. The high level differences in phylum abundance highlight the importance of well-designed sampling strategies for microbiome based studies. Results showed clear distinctions between Pekin Duck caecal contents and those of Broiler Chickens and Turkey in a qualitative comparison. These data provide a reference point for studies of the Pekin Duck through industry grow-out ages, provide a foundation for understanding the types of bacteria that promote health, and may lead to improved methods to increase yields and decrease instances of disease in agricultural production processes.

The dynamics of the human infant gut microbiome in development and in progression toward type 1 diabetes.

Colonization of the fetal and infant gut microbiome results in dynamic changes in diversity, which can impact disease susceptibility. To examine the relationship between human gut microbiome dynamics throughout infancy and type 1 diabetes (T1D), we examined a cohort of 33 infants genetically predisposed to T1D. Modeling trajectories of microbial abundances through infancy revealed a subset of microbial relationships shared across most subjects. Although strain composition of a given species was highly variable between individuals, it was stable within individuals throughout infancy. Metabolic composition and metabolic pathway abundance remained constant across time. A marked drop in alpha-diversity was observed in T1D progressors in the time window between seroconversion and T1D diagnosis, accompanied by spikes in inflammation-favoring organisms, gene functions, and serum and stool metabolites. This work identifies trends in the development of the human infant gut microbiome along with specific alterations that precede T1D onset and distinguish T1D progressors from nonprogressors.