Gastrointestinal Tract Microbiome Research Articles

Spatial profiles of the bacterial microbiota throughout the gastrointestinal tract of dairy goats

The gastrointestinal tract (GIT) is stationed by a dynamic and complex microbial community with functions in digestion, metabolism, immunomodulation, and reproduction. However, there is relatively little research on the composition and function of microorganisms in different GIT segments in dairy goats. Herein, 80 chyme samples were taken from ten GIT sites of eight Xinong Saanen dairy goats and then analyzed and identified the microbial composition via 16S rRNA V1-V9 amplicon sequencing. A total of 6669 different operational taxonomic units (OTUs) were clustered, and 187 OTUs were shared by ten GIT segments. We observed 264 species belonging to 23 different phyla scattered across ten GITs, with Firmicutes (52.42%) and Bacteroidetes (22.88%) predominating. The results revealed obvious location differences in the composition, diversity, and function of the GIT microbiota. In LEfSe analysis, unidentified_Lachnospiraceae and unidentified_Succinniclassicum were significantly enriched in the four chambers of stomach, with functions in carbohydrate fermentation to compose short-chain fatty acids. Aeriscardovia, Candidatus_Saccharimonas, and Romboutsia were significantly higher in the foregut, playing an important role in synthesizing enzymes, amino acids, and vitamins and immunomodulation. Akkermansia, Bacteroides, and Alistipes were significantly abundant in the hindgut to degrade polysaccharides and oligosaccharides, etc. From rumen to rectum, α-diversity decreased first and then increased, while β-diversity showed the opposite trend. Metabolism was the major function of the GIT microbiome predicted by PICRUSt2, but with variation in target substrates along the regions. In summary, GIT segments play a decisive role in the composition and functions of microorganisms.Key points• The jejunum and ileum were harsh for microorganisms to colonize due to the presence of bile acids, enzymes, faster chyme circulation, etc., exhibiting the lowest α-diversity and the highest β-diversity.• Variability in microbial profiles between the three foregut segments was greater than four chambers of stomach and hindgut, with a higher abundance of Firmicutes dominating than others.• Dairy goats dominated a higher abundance of Kiritimatiellaeota than cows, which was reported to be associated with fatty acid synthesis.

Distinct Gastrointestinal and Reproductive Microbial Patterns in Female Holobiont of Infertility.

The microbiota is in symbiosis with the human body as a holobiont. Infertility conditions affect the female reproductive tract (FRT) and its resident microbiota. However, a disturbance in homeostasis could influence the FRT and other distal body sites, such as the gastrointestinal tract (GIT). We included 21 patients with endometriosis and other infertility-associated diseases with clinical profiles and biological samples from the FRT (endometrium, endometrial fluid, and vagina), and GIT samples (oral and feces). We performed a 16S rRNA analysis of site-specific microbial communities and estimated diversity metrics. The study found body site-specific microbial patterns in the FRT-GIT. In both study groups, Lactobacillus was the most shared Amplicon Sequence Variant (ASV), a precise identifier of microbial sequences, between endometrial and vagina samples. However, shared Gardnerella and Enterobacteriaceae ASVs were linked to other conditions but not endometriosis. Remarkably, Haemophilus was a specific GIT-shared taxon in endometriosis cases. In conclusion, infertility influences distinctly the FRT and GIT microbiomes, with endometriosis showing unique microbial characteristics. We proposed the concept of 'female holobiont' as a community that comprises the host and microbes that must maintain overall homeostasis across all body sites to ensure a woman's health. Insights into these microbial patterns not only advance our understanding of the pathophysiology of infertility but also open new avenues for developing microbe-based therapeutic interventions aimed at restoring microbial balance, thereby enhancing fertility prospects.

296 Effects of dietary antimicrobials on the ruminant gastrointestinal tract microbiome

Abstract Monensin, tylosin, and chlortetracycline (CTC) are antimicrobials frequently employed in high grain feedlot cattle diets to inhibit liver abscesses and enhance growth. However, increased public concerns regarding antibiotic resistance have created a pressing need to develop alternative strategies. A more mechanistic understanding of how antimicrobial drugs effect the microbiome in the ruminant gastrointestinal tract (GIT) may help develop effective alternatives. Therefore, the objective of this study was to determine changes in the GIT microbiome of grain-fed feedlot steers after antimicrobial drug administration. Thirty individually housed Angus x Simmental steers [body weight (BW) = 355 ± 16.8 kg] previously fed a 56% forage diet were immediately transitioned to a 93% concentrate diet and assigned to one of three treatments (10 steers/treatment): 1) control, without antibiotics, 2) 75 mg of tylosin and 200 mg of monensin per animal per day (TYLMON), and 3) 70 mg of CTC per animal per day. Fecal samples were collected on d 0, 7, 14, 28, 56, 112, and at slaughter and digesta were obtained from the rumen, jejunum, and cecum at slaughter. DNA was extracted from samples, amplified via 16S PCR, and sequenced. Jejunal samples had the least alpha diversity compared with ruminal, cecal, or fecal samples (P < 0.001). There were no differences in measures of alpha diversity in the ruminal, jejunal, or cecal digesta at slaughter (P ≥ 0.10). However, overall measures of alpha diversity (Shannon entropy, observed features) in feces were greater in CTC-fed steers (P ≤ 0.009) as well as in TYLMON-fed steers (P ≤ 0.04) compared with control steers. Measures of alpha diversity for all treatments decreased in feces from d 0 to 7, then increased from d 7 to slaughter (time effect, (P ≤ 0.001). There were no differences in fecal alpha diversity between treatment groups on d 0 (P ≥ 0.50), but by d 28 both TYLMON and CTC treated steers had greater fecal alpha diversity compared with the control steers (P ≤ 0.05). With regard to differential abundance, Phascolarctobacterium and Prevotellaceae UCG-003 were more abundant in feces of control steers relative to antimicrobial treated steers (P < 0.05). Bifidobacterium, Dorea, CAG-56, and Erysipelotrichaceae UCG-003, were the 4 genera found to be in the greatest abundance in the feces of TYLMON-fed relative to control steers (P < 0.05). Akkermansia, Succinivibrio, and Turicbacter were the 3 genera found to be in the greatest abundance in the feces of CTC-fed compared with control steers (P < 0.05). Taken together, these data suggest that differences in the microbiome associated with dietary antimicrobial treatment occur to a greater extent in the lower sections of the GIT, and that these changes in the microbiome occur after 28 d of feeding.

Critical complex network structures in animal gastrointestinal tract microbiomes

BackgroundLiving things from microbes to their hosts (plants, animals and humans) interact with each other, and their relationships may be described with complex network models. The present study focuses on the critical network structures, specifically the core/periphery nodes and backbones (paths of high-salience skeletons) in animal gastrointestinal microbiomes (AGMs) networks. The core/periphery network (CPN) mirrors nearly ubiquitous nestedness in ecological communities, particularly dividing the network as densely interconnected core-species and periphery-species that only sparsely linked to the core. Complementarily, the high-salience skeleton network (HSN) mirrors the pervasive asymmetrical species interactions (strictly microbial species correlations), particularly forming heterogenous pathways in AGM networks with both “backbones” and “rural roads” (regular or weak links). While the cores and backbones can act as critical functional structures, the periphery nodes and weak links may stabilize network functionalities through redundancy.ResultsHere, we build and analyze 36 pairs of CPN/HSN for the AGMs based on 4903 gastrointestinal-microbiome samples containing 473,359 microbial species collected from 318 animal species covering all vertebrate and four major invertebrate classes. The network analyses were performed at host species, order, class, phylum, kingdom scales and diet types with selected and comparative taxon pairs. Besides diet types, the influence of host phylogeny, measured with phylogenetic (evolutionary) timeline or “age”, were integrated into the analyses. For example, it was found that the evolutionary trends of three primary microbial phyla (Bacteroidetes/Firmicutes/Proteobacteria) and their pairwise abundance-ratios in animals do not mirror the patterns in modern humans phylogenetically, although they are consistent in terms of diet types.ConclusionsOverall, the critical network structures of AGMs are qualitatively and structurally similar to those of the human gut microbiomes. Nevertheless, it appears that the critical composition (the three phyla of Bacteroidetes, Firmicutes, and Proteobacteria) in human gut microbiomes has broken the evolutionary trend from animals to humans, possibly attributable to the Anthropocene epoch and reflecting the far-reaching influences of agriculture and industrial revolution on the human gut microbiomes. The influences may have led to the deviations between modern humans and our hunter-gather ancestors and animals.

Microbiome: Mammalian milk microbiomes: sources of diversity, potential functions, and future research directions.

Milk is an ancient, fundamental mammalian adaptation that provides nutrition and biochemical communication to offspring. Microbiomes have been detected in milk of all species studied to date. In this review, we discuss: (a) routes by which microbes may enter milk; (b) evidence for proposed milk microbiome adaptive functions; (c) variation in milk microbiomes across mammals; and (d) future research directions, including suggestions for how to address outstanding questions on the viability and functionality of milk microbiomes. Milk microbes may be sourced from the maternal gastrointestinal tract, oral, skin, and mammary gland microbiomes and from neonatal oral and skin microbiomes. Given the variety of microbial sources, stochastic processes strongly influence milk microbiome assembly, but milk microbiomes appear to be influenced by maternal evolutionary history, diet, environment, and milk nutrients. Milk microbes have been proposed to colonize the neonatal intestinal tract and produce gene and metabolic products that influence physiology, metabolism, and immune system development. Limited epidemiological data indicate that early-life exposure to milk microbes can result in positive, long-term health outcomes. Milk microbiomes can be modified by dietary changes including providing the mother with probiotics and prebiotics. Milk replacers (i.e. infant formula) may benefit from supplementation with probiotics and prebiotics, but data are lacking on probiotics' usefulness, and supplementation should be evidence based. Overall, milk microbiome literature outside of human and model systems is scarce. We highlight the need for mechanistic studies in model species paired with comparative studies across mammals to further our understanding of mammalian milk microbiome evolution. A broader study of milk microbiomes has the potential to inform animal care with relevance to ex situ endangered species. Milk is an ancient adaptation that supports the growth and development of mammalian neonates and infants. Beyond its fundamental nutritional function, milk influences all aspects of neonatal development, especially immune function. All kinds of milks so far studied have contained a milk microbiome. In this review, we focus on what is known about the collection of bacterial members found in milk microbiomes. Milk microbiomes include members sourced from maternal and infant microbiomes and they appear to be influenced by maternal evolutionary history, diet, milk nutrients, and environment, as well as by random chance. Once a neonate begins nursing, microbes from milk colonize their gut and produce byproducts that influence their physiology, metabolism, and immune development. Empirical data on milk microbiomes outside of humans and model systems are sparse. Greater study of milk microbiomes across mammals will expand our understanding of mammalian evolution and improve the health of animals under human care.

Acute Impacts of Ionizing Radiation Exposure on the Gastrointestinal Tract and Gut Microbiome in Mice.

Radiation therapy for abdominopelvic malignancies often results in damage to the gastrointestinal tract (GIT) and permanent changes in bowel function. An overlooked component of the pathophysiology of radiation-induced bowel injury is the role of the gut microbiome. The goal of this research was to identify the impacts of acute radiation exposure on the GIT and gut microbiome. C57BL/6 mice exposed to whole-body X-rays (0.1-3 Gy) were assessed for histological and microbiome changes 48 h post-radiation exposure. Within the ileum, a dose of 3 Gy significantly decreased crypt depth as well as the number of goblet cells, but increased overall goblet cell size. Overall, radiation altered the microbial distribution within each of the main phyla in a dose- and tissue-dependent manner. Within the Firmicutes phylum, high dose irradiation resulted in significant alterations in bacteria from the class Bacilli within the small bowels, and from the class Clostridia in the large bowels. The 3 Gy radiation also significantly increased the abundance of bacterial families from the Bacteroidetes phylum in the colon and feces. Overall, we identified various alterations in microbiome composition following acute radiation exposure, which could potentially lead to novel biomarkers for tracking patient toxicities or could be used as targets for mitigation strategies against radiation damage.

Effect of a Lactobacilli-Based Direct-Fed Microbial Product on Gut Microbiota and Gastrointestinal Morphological Changes.

The calf's gastrointestinal tract (GIT) microbiome undergoes rapid shifts during early post-natal life, which can directly affect calf performance. The objectives of this study were to characterise and compare differences in the establishment and succession of GIT microbiota, GIT morphological changes, and the growth of dairy calves from birth until weaned. Forty-four newborn Holstein-Friesian calves were randomly selected and assigned to Treatment (TRT) and Control (CON) groups. The TRT group calves received a once-daily dose of a direct-fed microbial (DFM) liquid product containing Lacticaseibacillus paracasei, Lentilactobacillus buchneri, and Lacticaseibacillus casei, all formerly known as Lactobacillus. Fresh faecal samples were manually taken from the rectum of all calves, and gross necropsy was performed on the forestomachs and gastrointestinal tracts. Bacterial DNA was extracted from frozen faecal samples for 16S rRNA gene amplicon sequencing. Calves in the TRT group had greater live weights (p = 0.02) at weaning compared with calves in the CON group (mean = 69.18 kg, SD = 13.37 kg). The average daily live weight gain (ADG) and total feed intake were similar between the two groups. Calves in the TRT group had greater duodenum, abomasum, and reticulum weights (p = 0.05). Rumen and intestinal development (p < 0.05) and faecal microbial diversity (p < 0.05) were more pronounced in the TRT group. The relative abundances of eight genera differed (p < 0.001) between the groups. Supplementing calves with the LAB-based DFM increased live weight at weaning and had a more pronounced effect on the development of rumen and the gastrointestinal tract and on microbiota diversity and evenness. Future work is needed to better understand the potential association of LAB-DFM products on gut mucosa-associated microbiota.

Ecological niches and assembly dynamics of diverse microbial consortia in the gastrointestine of goat kids.

Goats are globally invaluable ruminants that balance food security and environmental impacts, and their commensal microbiome residing in the gastrointestinal tract (GIT) is associated with animal health and productivity. However, the reference genomes and functional repertoires of GIT microbes in goat kids have not been fully elucidated. Herein, we performed a comprehensive landscape survey of the GIT microbiome of goat kids using metagenomic sequencing and binning, spanning a dense sampling regime covering three gastrointestinal compartments spatially and five developmental ages temporally. We recovered 1002 high-quality metagenome-assembled genomes (termed the goat kid GIT microbial catalog [GKGMC]), 618 of which were novel. They encode more than 2.3 million nonredundant proteins, and represent a variety of carbohydrate-degrading enzymes and metabolic gene clusters. The GKGMC-enriched microbial taxa, particularly Sodaliphilus, expanded the microbial tree of life in goat kids. Using this GKGMC, we first deciphered the prevalence of fiber-degrading bacteria for carbohydrate decomposition in the rumen and colon, while the ileal microbiota specialized in the uptake and conversion of simple sugars. Moreover, GIT microorganisms were rapidly assembled after birth, and their carbohydrate metabolic adaptation occurred in three phases of progression. Finally, phytobiotics modified the metabolic cascades of the ileal microbiome, underpinned by the enrichment of Sharpea azabuensis and Olsenella spp. implicated in lactate formation and utilization. This GKGMC reference provides novel insights into the early-life microbial developmental dynamics in distinct compartments, and offers expanded resources for GIT microbiota-related research in goat kids.

Microbiome Changes in Layer Pullets Reared in Floor Pens along the Growth Period.

The gastrointestinal tract microbiome is essential for regulating nutrient absorption, gut immune function, and host growth and development. In the present study, we characterized the development of ileum and cecum microbiota in pullets throughout the rearing period, encompassing a period from the day of hatching to 18 weeks of age. The growth performance and intestinal microbiome (ileum and cecum) of pullets were analyzed at 1, 5, 11, and 18 weeks of age. The richness of the ileum and cecum bacterial communities (alpha diversity) was higher in pullets at 18 weeks of age than in those at 1 and 5 weeks of age. Microbiota from weeks 1, 5, 11, and 18 were distinctly grouped in a NMDS plot, representing beta diversity within the ileum. However, the results for cecum microbiota did not reveal evident separation among the different age groups in the weighted UniFrac. In conclusion, our findings demonstrate variations and diversification in ileum and cecum microbiota across different rearing stages in pullets. These insights have the potential to inform the development of nutritional strategies that promote gut health and contribute to the improved development of pullets.

Establishing the link between microbial communities in bovine liver abscesses and the gastrointestinal tract

BackgroundLiver abscesses (LAs) are one of the most common and important problems faced by the beef industry. The most efficacious method for the prevention of LAs in North America is through dietary inclusion of low doses of antimicrobial drugs such as tylosin, but the mechanisms by which this treatment prevents LAs are not fully understood. LAs are believed to result from mucosal barrier dysfunction in the gastrointestinal tract (GIT) allowing bacterial translocation to the liver via the portal vein, yet differences in the GIT microbiome of cattle with and without LAs have not been explored. Here, we characterized microbial communities from LAs, rumen, ileum, and colon from the same cattle for the first time.ResultsResults demonstrate that tylosin supplementation was associated with differences in microbial community structure in the rumen and small intestine, largely because of differences in the predominance of Clostridia. Importantly, we show for the first time that microbial communities from multiple LAs in one animal’s liver are highly similar, suggesting that abscesses found at different locations in the liver may originate from a localized source in the GIT (rather than disparate locations). A large portion of abscesses were dominated by microbial taxa that were most abundant in the hindgut. Further, we identified taxa throughout the GIT that were differentially abundant between animals with and without liver abscesses. Bifidobacterium spp.—a bacteria commonly associated with a healthy GIT in several species—were more abundant in the rumen and ileum of animals without LAs compared to those with LAs.ConclusionsTogether these results provide the first direct comparison of GIT and LA microbial communities within the same animal, add considerable evidence to the hypothesis that some LA microbial communities arise from the hindgut, and suggest that barrier dysfunction throughout the GIT may be the underlying cause of LA formation in cattle.

Gut–Skin Axis: Gut Microbiota as a Link Between Rosacea and Gastrointestinal Comorbidities

Abstract: Rosacea, a prevalent dermatological condition, is characterized by the clinical manifestations of erythema, papules, and pustules. This paper delves into the emerging role of the gut-skin axis in Rosacea's pathophysiology. Convincing evidence supports the involvement of gut microbiota in orchestrating the inflammatory cutaneous response. Its multifaceted etiology is thought to be influenced by genetic susceptibility, alterations in the neurovascular and immune systems, and altered interactions with the microbiota. Strong connections broaden our understanding of Rosacea, linking it to neurological conditions like Parkinson's disease and gastrointestinal issues such as Helicobacter pylori infection and small intestinal bacterial overgrowth (SIBO), supporting the existence of an intricate brain-gut-skin connection. The interplay between these organs' homeostatic and regulatory systems is increasingly evident. While we have not fully grasped the details of immunological, neuroendocrine, and metabolic pathways, it is clear they play a part in chronic inflammatory skin conditions like Rosacea. Delving into these intricate pathways promises a nuanced comprehension of the disease's etiopathogenesis. An in-depth investigation into the roles of dysbiotic microbiota and dysregulated innate immune responses is imperative to comprehensively fathom Rosacea's pathophysiological landscape. A refined grasp of this condition and the gutskin axis holds the potential for optimizing therapeutic trajectories. The purpose of this review is to explore potential bacterial indicators of the disease and to assess whether the gut microbiome makeup of individuals with inflammatory Rosacea differs from that of healthy controls. Furthermore, it critically assesses and consolidates previously documented alterations in peripheral blood, skin, and gastrointestinal tract microbiomes within rosacea patients. This review illuminates the intricate dance of microbiota in the context of Rosacea, forging a bridge between cutting-edge insights and its implications. By synthesizing current knowledge, this review advances our understanding of microbiota-driven mechanisms in inflammatory Rosacea, paving the way for innovative therapeutic strategies.

MICROBIOMES OF HUMAN, LIVESTOCK ANIMAL GASTROINTESTINAL TRACTS AND OF FOOD PRODUCTS AND COMPOUND FEEDS: CONNECTIONS AND IMPACTS. PART 1

The physiological mechanisms of food digestion in humans and feed digestion in animals are determined by the structure of the gastrointestinal tract (GIT) and diet. Accordingly, humans are omnivores, while domestic animals are divided into ruminants, monogastric herbivores, and monogastric omnivores, and birds are divided into herbivores (geese, ducks) and omnivores (chickens, turkeys, etc.). The digestion and assimilation of food and feed depends not only on own mechanisms but also on the GIT microbiome. The location of the most important part of this microbiome and its composition depend on the species: in ruminants, it is the rumen microbiome, in horses – the cecum (it is a counterpart of the rumen), in humans and pigs – the intestine, in birds – the crop, gizzard and cecum. These microbiomes are in constant close connection with the host organism, and this connection is realized through numerous molecular mechanisms of interaction between bacterial cells and host cells and tissues. GIT microorganisms not only help to assimilate food (feed) by partially digesting it, but also secrete biologically active substances that have protective, stimulating and other beneficial effects for the host. In adult hosts, this GIT microbiota is well developed and stable, while in children and young animals it can be much more mobile and vulnerable. Food and feed contain many components that are a favorable medium for the development of microorganisms. Raw materials and components of animal origin are the most contaminated, while vegetable raw materials and components, as well as premixes, contain significantly fewer microorganisms. Among the microorganisms colonizing raw materials, food and feeds, coliforms, salmonellae and molds may be present. In young animals, the feed microbiota ingested into the GIT, even without taking into account obligate or opportunistic pathogens, can cause shifts or changes in the digestive microenvironment towards deterioration, which will have a corresponding impact on the efficiency of feed absorption and, through it, on the efficiency of feeding and animal productivity.

90 Microbiome-Derived Bioactive Molecules to Reduce Enteric Methane Emissions

Abstract Microorganisms are pivotal for the development, health, and productivity of livestock. In adult ruminants, the microbiota colonizing the rumen is essential for efficient depolymerization of indigestible carbohydrates from plant biomass and their conversion into microbial protein and fermentation end-products that are used by the host for growth. In the last decades, next-generation sequencing and omics technologies provided unparalleled insights into the composition, structure, and function of the gastrointestinal (GI) tract microbiome of ruminants and helped improve our understanding of relationships between the rumen microbiota with cattle performance (efficiency) traits, as well as health and disease and greenhouse gas emissions. The ecological interactions between microbes within the rumen ecosystem are complex and involve, among others, cross-feeding, predation, parasitism, antagonism, and competition for novel (empty) niches and available resources. These diverse associations of ecological traits across distinct microbial populations that coexist in the same ecosystem represent a goldmine for the discovery of novel bioactive molecules, including compounds with potential to modulate rumen fermentation and inhibit methane emissions from enteric fermentation. These effects often result from metabolic shifts in the rumen fermentation that lead to increased production of propionate, but can also be caused by direct inhibition of methanogenic archaea or through a reduction in the production of substrates for methanogenesis. Culture-independent approaches based on genome mining and functional metagenomics demonstrated that the rumen is an underexplored resource for bioactive molecules, such as antimicrobial peptides, non-ribosomal peptides, polyketides, and secondary metabolites involved in intercellular (microbe-microbe) communication. Rumen metatranscriptomic data indicate that the expression of genes potentially encoding some of these molecules is increased during the colonization of plant biomass that enters the rumen. Nonetheless, some representatives of key taxa from the core rumen microbiome cannot be found in culture collections, which is critical to validate phenotypic predictions from genomic and metagenomic data and obtain ecological insights about the interplay between individual microbial populations in the microbiome. Culturomic technologies and high-throughput identification and characterization of microbial species that colonize the rumen could contribute to building a unique biotechnological resource that can be explored for sourcing novel bioactive compounds with anti-methanogenic activity and developing fermentation products that could reduce rumen methanogenesis while improving the health status and productivity of cattle.

Erythrocytic α-Synuclein and the Gut Microbiome: Kindling of the Gut-Brain Axis in Parkinson's Disease.

Progressive spreading of α-synuclein via gut-brain axis has been hypothesized in the pathogenesis of Parkinson's disease (PD). However, the source of seeding-capable α-synuclein in the gastrointestinal tract (GIT) has not been fully investigated. Additionally, the mechanism by which the GIT microbiome contributes to PD pathogenesis remains to be characterized. We aimed to investigate whether blood-derived α-synuclein might contribute to PD pathology via a gut-driven pathway and involve GIT microbiota. The GIT expression of α-synuclein and the transmission of extracellular vesicles (EVs) derived from erythrocytes/red blood cells (RBCs), with their cargo α-synuclein, to the GIT were explored with various methods, including radioactive labeling of RBC-EVs and direct analysis of the transfer of α-synuclein protein. The potential role of microbiota on the EVs transmission was further investigated by administering butyrate, the short-chain fatty acids produced by gut microbiota and studying mice with different α-synuclein genotypes. This study demonstrated that RBC-EVs can effectively transport α-synuclein to the GIT in a region-dependent manner, along with variations closely associated with regional differences in the expression of gut-vascular barrier markers. The investigation further revealed that the infiltration of α-synuclein into the GIT was influenced significantly by butyrate and α-synuclein genotypes, which may also affect the GIT microbiome directly. By demonstrating the transportation of α-synuclein through RBC-EVs to the GIT, and its potential association with gut-vascular barrier markers and gut microbiome, this work highlights a potential mechanism by which RBC α-synuclein may impact PD initiation and/or progression. © 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Sodium butyrate promotes gastrointestinal development of preweaning bull calves via inhibiting inflammation, balancing nutrient metabolism, and optimizing microbial community functions.

Butyrate promotes the growth and gastrointestinal development of calves. But, the mechanisms behind its effects on signaling pathways of the gastrointestinal tract and rumen microbiome is unclear. This study aimed to reveal transcriptomic pathways of gastrointestinal epithelium and microbial community in response to butyrate supplementation in calves fed a high fiber starter. Fourteen Holstein bull calves (39.9±3.7kg, 14d of age) were assigned to 2 groups (sodium butyrate group, SB; control group, Ctrl). The SB group received 0.5% SB supplementation. At d 51, the calves were slaughtered to obtain samples for analysis of the transcriptome of the rumen and jejunum epithelium as well as ruminal microbial metagenome. Sodium butyrate supplementation resulted in a higher performance in average daily gain and development of jejunum and rumen papillae. In both the rumen and jejunum epithelium, SB down-regulated pathways related to inflammation including NF-κB (PPKCB, CXCL8, CXCL12), interleukin-17 (IL17A, IL17B, MMP9), and chemokine (CXCL12, CCL4, CCL8) and up-regulated immune pathways including the intestinal immune network for immunoglobulin A (IgA) production (CD28). Meanwhile, in the jejunum epithelium, SB regulated pathways related to nutritional metabolism including nitrogen metabolism (CA1, CA2, CA3), synthesis and degradation of ketone bodies (HMGCS2, BDH1, LOC100295719), fat digestion and absorption (PLA2G2F, APOA1, APOA4), and the PPAR signaling pathway (FABP4, FABP6, CYP4A11). The metagenome showed that SB greatly increased the relative abundance of Bacillus subtilis and Eubacterium limosum, activated ruminal microbial carbohydrate metabolism pathways and increased the abundance of carbohydrate hydrolysis enzymes. In conclusion, butyrate exhibited promoting effects on growth and gastrointestinal development by inhibiting inflammation, enhancing immunity and energy harvesting, and activating microbial carbohydrate metabolism. These findings provide new insights into the potential mechanisms behind the beneficial effects of butyrate in calf nutrition.

The use of diet for preventing and treating depression in young men: current evidence and existing challenges.

Emerging evidence suggests that diet therapy (nutrients, foods and dietary patterns) could be effective as a potential adjunctive treatment option for major depressive disorder. Numerous mechanisms have been proposed, including the role inflammation, oxidative stress, brain-derived neurotrophic factor, the gastrointestinal tract microbiome and tryptophan/serotonin metabolism. Despite known differences in depression characteristics and treatment responses between males and females, there are limited sex-specific studies examining the role of diet in young men specifically. This is important as young men are often reluctant to seek mental health support, so finding treatment strategies which appeal to this demographic is crucial. This brief report provides an overview of the most recent advances in the use of diet for preventing and treating depression in young men, highlighting existing challenges and opportunities for future research. We recommend that clinicians discuss the role of diet with depressed young men, so that diet may be used alongside current treatment options.

A phase 1b study to evaluate the efficacy, safety, and pharmacokinetics of an investigational microbiome therapeutic, SER-155, in adults undergoing hematopoietic stem cell transplantation.

TPS7080 Background: In patients undergoing allogeneic hematopoietic cell transplantation (HCT), loss of gastrointestinal microbial diversity is associated with risk of bloodstream infections (BSI), acute graft-versus-host disease (aGvHD), and death. SER-155 is a rationally designed investigational cultivated microbiome therapeutic, hypothesized to improve clinical outcomes in HCT by restoring colonization resistance to potential pathogens, promoting epithelial barrier integrity, and reducing colonic inflammation. SER-155-001 is a Phase 1b study evaluating the efficacy, safety, and pharmacokinetics (PK) of SER-155 in adults undergoing HCT. Methods: This study will enroll approximately 70 subjects ≥18 years in an open-label Cohort 1 (n = 10) followed by a double-blind, placebo-controlled Cohort 2 (n = 60) randomized 1:1 to SER-155 or placebo. A variety of conditioning regimens, donor types, and GVHD-prophylaxis regimens are included. Exclusion criteria include history of severe colitis or active inflammatory bowel disease or total colectomy, umbilical cord blood or ex vivo T-cell depletion, exposure to fecal microbiota transplant or any live microbial therapeutic within 3 months prior to screening, and evidence of relapse or progression of hematologic malignancy (minimal residual disease is allowed). Following screening, participants in both cohorts receive 2 treatment courses (one before and one after HCT), each comprised of microbiome conditioning with oral vancomycin or placebo followed by SER-155 or placebo, plus a conditional 3rd treatment course if the subject receives antibiotics. Safety outcomes are followed through 52 weeks post HCT. The primary endpoint is the incidence and severity of adverse events, serious adverse events, and adverse events of special interest. Secondary endpoints include rates of BSI, gastrointestinal infections, aGvHD, febrile neutropenia and overall survival. Microbiome related endpoints include engraftment of SER-155 bacterial strains in the gastrointestinal tract (PK endpoint) and fecal microbiome diversity, composition and metabolites. Results: Cohort 1 enrollment is complete, with 13 participants receiving SER-155. In December 2022, the Data and Safety Monitoring Committee supported continuation to Cohort 2 enrollment following review of safety data from Cohort 1. Enrollment in Cohort 2 is underway. Conclusions: This Phase 1b study is designed to assess the safety, and clinical efficacy of SER-155 in allogeneic HCT, expanding the clinical experience of microbiome- directed interventions in allogeneic HCT recipients. Clinical trial information: NCT04995653 .

Evidence of a divided nutritive function in rainbow Trout (Oncorhynchus mykiss) midgut and hindgut microbiomes by whole shotgun metagenomic approach

The nutritive role and ecology of gut-dwelling microbes in rainbow trout remain enigmatic. To improve our understanding of the rainbow trout gastrointestinal tract (GIT) microbiome, we performed whole shotgun metagenomic analyses on the assembled contigs from luminal contents from both mid- and hind-GIT regions for taxonomic and functional classifications of fish-fed animal and plant protein dietary sources. Our study revealed that trout respond well to the two diets containing animal and plant protein sources when supplemented with essential amino acids to meet the requirements of the fish. Microbes present were predominantly bacteria (89.9%) and mainly of the phyla Tenericutes, Firmicutes, Fusobacteria, and Proteobacteria. Eukaryotic (8.8%) microbes were mainly from phyla Ascomycota and Basidiomycota, while Archaea (<1%) were also present and predominantly from the phylum Euryarchaeota. Comparisons of genus-level classifications and functional profiles revealed compositional differences in these GIT locations that appear modulated by differences in the dietary treatments. The functional analysis provided evidence of amino acid biosynthesis/catabolism and methane production in the mid-GIT, while in the hind-GIT, proteolytic hydrolysis and butyrate metabolism were expressed in the trout fed with plant protein diet. The animal protein-based diet provided metabolites for microbial protein fermentation in the hind-GIT. Our report highlights and identifies the potential nutritive contributions of GIT microbes to trout and a potentially crucial functional division along the GIT. Finally, the plant-based diet enhanced amino acid catabolism in the midgut section, while the hindgut section supports evidence of methanogen fermentation.

Unveiling the Human Gastrointestinal Tract Microbiome: The Past, Present, and Future of Metagenomics

Over 1014 symbiotic microorganisms are present in a healthy human body and are responsible for the synthesis of vital vitamins and amino acids, mediating cellular pathways and supporting immunity. However, the deregulation of microbial dynamics can provoke diverse human diseases such as diabetes, human cancers, cardiovascular diseases, and neurological disorders. The human gastrointestinal tract constitutes a hospitable environment in which a plethora of microbes, including diverse species of archaea, bacteria, fungi, and microeukaryotes as well as viruses, inhabit. In particular, the gut microbiome is the largest microbiome community in the human body and has drawn for decades the attention of scientists for its significance in medical microbiology. Revolutions in sequencing techniques, including 16S rRNA and ITS amplicon sequencing and whole genome sequencing, facilitate the detection of microbiomes and have opened new vistas in the study of human microbiota. Especially, the flourishing fields of metagenomics and metatranscriptomics aim to detect all genomes and transcriptomes that are retrieved from environmental and human samples. The present review highlights the complexity of the gastrointestinal tract microbiome and deciphers its implication not only in cellular homeostasis but also in human diseases. Finally, a thorough description of the widely used microbiome detection methods is discussed.

Trophic level and proteobacteria abundance drive antibiotic resistance levels in fish from coastal New England

BackgroundThe natural marine environment represents a vast reservoir of antimicrobial resistant bacteria. The wildlife that inhabits this environment plays an important role as the host to these bacteria and in the dissemination of resistance. The relationship between host diet, phylogeny, and trophic level and the microbiome/resistome in marine fish is not fully understood. To further explore this relationship, we utilize shotgun metagenomic sequencing to define the gastrointestinal tract microbiomes of seven different marine vertebrates collected in coastal New England waters.ResultsWe identify inter and intraspecies differences in the gut microbiota of these wild marine fish populations. Furthermore, we find an association between antibiotic resistance genes and host dietary guild, which suggests that higher trophic level organisms have a greater abundance of resistance genes. Additionally, we demonstrate that antibiotic resistance gene burden is positively correlated with Proteobacteria abundance in the microbiome. Lastly, we identify dietary signatures within the gut of these fish and find evidence of possible dietary selection for bacteria with specific carbohydrate utilization potential.ConclusionsThis work establishes a link between host lifestyle/dietary guild, and microbiome composition and the abundance of antibiotic resistance genes within the gastrointestinal tract of marine organisms. We expand the current understanding of marine organism-associated microbial communities and their role as reservoirs of antimicrobial resistance genes.