Gut Ecosystem Research Articles

Intrahost evolution of the gut microbiota.

A massive number of microorganisms, belonging to different species, continuously divide inside the guts of animals and humans. The large size of these communities and their rapid division times imply that we should be able to watch microbial evolution in the gut in real time, in a similar manner to what has been done in vitro. Here, we review recent findings on how natural selection shapes intrahost evolution (also known as within-host evolution), with a focus on the intestines of mice and humans. The microbiota of a healthy host is not as static as initially thought from the information measured at only one genomic marker. Rather, the genomes of each gut-colonizing species can be highly dynamic, and such dynamism seems to be related to the microbiota species diversity. Genetic and bioinformatic tools, and analysis of time series data, allow quantification of the selection strength on emerging mutations and horizontal transfer events in gut ecosystems. The drivers and functional consequences of gut evolution can now begin to be grasped. The rules of this intrahost microbiota evolution, and how they depend on the biology of each species, need to be understood for more effective development of microbiota therapies to help maintain or restore host health.

Quantifying Shared and Unique Gene Content across 17 Microbial Ecosystems.

Measuring microbial diversity is traditionally based on microbe taxonomy. Here, in contrast, we aimed to quantify heterogeneity in microbial gene content across 14,183 metagenomic samples spanning 17 ecologies, including 6 human associated, 7 nonhuman host associated, and 4 in other nonhuman host environments. In total, we identified 117,629,181 nonredundant genes. The vast majority of genes (66%) occurred in only one sample (i.e., "singletons"). In contrast, we found 1,864 sequences present in every metagenome, but not necessarily every bacterial genome. Additionally, we report data sets of other ecology-associated genes (e.g., abundant in only gut ecosystems) and simultaneously demonstrated that prior microbiome gene catalogs are both incomplete and inaccurately cluster microbial genetic life (e.g., at gene sequence identities that are too restrictive). We provide our results and the sets of environmentally differentiating genes described above at http://www.microbial-genes.bio. IMPORTANCE The amount of shared genetic elements has not been quantified between the human microbiome and other host- and non-host-associated microbiomes. Here, we made a gene catalog of 17 different microbial ecosystems and compared them. We show that most species shared between environment and human gut microbiomes are pathogens and that prior gene catalogs described as "nearly complete" are far from it. Additionally, over two-thirds of all genes only appear in a single sample, and only 1,864 genes (0.001%) are found in all types of metagenomes. These results highlight the large diversity between metagenomes and reveal a new, rare class of genes, those found in every type of metagenome, but not every microbial genome.

Modulating the Microbiome for Crohn’s Disease Treatment

The central role of the gut microbiota in the regulation of health and disease has been convincingly demonstrated. Polymicrobial interkingdom interactions between bacterial (the bacteriome) and fungal (the mycobiome) communities of the gut have become a prominent focus for development of potential therapeutic approaches. In addition to polymicrobial interactions, the complex gut ecosystem also mediates interactions between the host and the microbiota. These interactions are complex and bidirectional; microbiota composition can be influenced by host immune response, disease-specific therapeutics, antimicrobial drugs, and overall ecosystems. However, the gut microbiota also influences host immune response to a drug or therapy by potentially transforming the drug's structure and altering bioavailability, activity, or toxicity. This is especially true in cases where the gut microbiota has produced a biofilm. The negative ramifications of biofilm formation include alteration of gut permeability, enhanced antimicrobial resistance, and alteration of host immune response effectiveness. Natural modulation of the gut microbiota, using probiotic and prebiotic approaches, may also be used to affect the host microbiome, a type of "natural" modulation of the host microbiota composition. In this review, we discuss potential bidirectional interactions between microbes and host, and we describe the changes in gut microbiota induced by probiotic and prebiotic approaches as well as their potential clinical consequences, including biofilm formation. We outline a systematic approach to designing probiotics capable of altering the host microbiota in disease states, using Crohn's disease as a model chronic disease. Understanding how the effective changes in the microbiome may enhance treatment efficacy may unlock the possibility of modulating the gut microbiome to improve treatment using a natural approach.

Impact of High Salt-Intake on a Natural Gut Ecosystem in Wildling Mice.

The mammalian holobiont harbors a complex and interdependent mutualistic gut bacterial community. Shifts in the composition of this bacterial consortium are known to be a key element in host health, immunity and disease. Among many others, dietary habits are impactful drivers for a potential disruption of the bacteria-host mutualistic interaction. In this context, we previously demonstrated that a high-salt diet (HSD) leads to a dysbiotic condition of murine gut microbiota, characterized by a decrease or depletion of well-known health-promoting gut bacteria. However, due to a controlled and sanitized environment, conventional laboratory mice (CLM) possess a less diverse gut microbiota compared to wild mice, leading to poor translational outcome for gut microbiome studies, since a reduced gut microbiota diversity could fail to depict the complex interdependent networks of the microbiome. Here, we evaluated the HSD effect on gut microbiota in CLM in comparison to wildling mice, which harbor a natural gut ecosystem more closely mimicking the situation in humans. Mice were treated with either control food or HSD and gut microbiota were profiled using amplicon-based methods targeting the 16S ribosomal gene. In line with previous findings, our results revealed that HSD induced significant loss of alpha diversity and extensive modulation of gut microbiota composition in CLM, characterized by the decrease in potentially beneficial bacteria from Firmicutes phylum such as the genera Lactobacillus, Roseburia, Tuzzerella, Anaerovorax and increase in Akkermansia and Parasutterella. However, HSD-treated wildling mice did not show the same changes in terms of alpha diversity and loss of Firmicutes bacteria as CLM, and more generally, wildlings exhibited only minor shifts in the gut microbiota composition upon HSD. In line with this, 16S-based functional analysis suggested only major shifts of gut microbiota ecological functions in CLM compared to wildling mice upon HSD. Our findings indicate that richer and wild-derived gut microbiota is more resistant to dietary interventions such as HSD, compared to gut microbiota of CLM, which may have important implications for future translational microbiome research.

Elucidating dynamic anaerobe metabolism with HRMAS 13C NMR and genome-scale modeling

Anaerobic microbial metabolism drives critical functions within global ecosystems, host–microbiota interactions, and industrial applications, yet remains ill-defined. Here we advance a versatile approach to elaborate cellular metabolism in obligate anaerobes using the pathogen Clostridioides difficile, an amino acid and carbohydrate-fermenting Clostridia. High-resolution magic angle spinning nuclear magnetic resonance (NMR) spectroscopy of C. difficile, grown with fermentable 13C substrates, informed dynamic flux balance analysis (dFBA) of the pathogen’s genome-scale metabolism. Analyses identified dynamic recruitment of oxidative and supporting reductive pathways, with integration of high-flux amino acid and glycolytic metabolism at alanine’s biosynthesis to support efficient energy generation, nitrogen handling and biomass generation. Model predictions informed an approach leveraging the sensitivity of 13C NMR spectroscopy to simultaneously track cellular carbon and nitrogen flow from [U-13C]glucose and [15N]leucine, confirming the formation of [13C,15N]alanine. Findings identify metabolic strategies used by C. difficile to support its rapid colonization and expansion in gut ecosystems.

Body Metrics and the Gut Microbiome in Response to Macronutrient Limitation in the Zebrafish Danio rerio

BackgroundHealthy and predictable physiologic homeostasis is paramount in animal models for biomedical research. Proper macronutrient intake is an essential and controllable environmental factor for maintaining animal health and promoting experimental reproducibility. Objective and MethodsEvaluate reductions in dietary macronutrient composition on body weight metrics, composition, and gut microbiome in Danio rerio. MethodsD. rerio were fed reference diets deficient in either protein or lipid content for 14 weeks. ResultsDiets of reduced-protein or reduced-fat resulted in lower weight gain than the standard reference diet in male and female D. rerio. Females fed the reduced-protein diet had increased total body lipid, suggesting increased adiposity compared with females fed the standard reference diet. In contrast, females fed the reduced-fat diet had decreased total body lipid compared with females fed the standard reference diet. The microbial community in male and female D. rerio fed the standard reference diet displayed high abundances of Aeromonas, Rhodobacteraceae, and Vibrio. In contrast, Vibrio spp. were dominant in male and female D. rerio fed a reduced-protein diet, whereas Pseudomonas displayed heightened abundance when fed the reduced-fat diet. Predicted functional metagenomics of microbial communities (PICRUSt2) revealed a 3- to 4-fold increase in the KEGG (Kyoto Encyclopedia of Genes and Genomes) functional category of steroid hormone biosynthesis in both male and female D. rerio fed a reduced-protein diet. In contrast, an upregulation of secondary bile acid biosynthesis and synthesis and degradation of ketone bodies was concomitant with a downregulation in steroid hormone biosynthesis in females fed a reduced-fat diet. ConclusionsThese study outcomes provide insight into future investigations to understand nutrient requirements to optimize growth, reproductive, and health demographics to microbial populations and metabolism in the D. rerio gut ecosystem. These evaluations are critical in understanding the maintenance of steady-state physiologic and metabolic homeostasis in D. rerio. Curr Dev Nutr 20xx;x:xx.

Microbiome Structure and Mucosal Morphology of Jejunum Appendix and Colon of Rats in Health and Dysbiosis

Gut microbiota contributes to human health. Plenty of studies demonstrate that antibiotics can disrupt gut ecosystem leading to dysbiosis. Little is known about the microbial variation of appendix and its up/downstream intestine after antibiotic treatment. This study aimed to investigate the microbiome and mucosal morphology of jejunum, appendix, and colon of rats in health and dysbiosis. A rodent model of antibiotic-induced dysbiosis was employed. Microscopy was used to observe mucosal morphological changes. 16S rRNA sequencing was performed for identifying bacterial taxa and microbiome structure. The appendices of dysbiosis were found enlarged and inflated with loose contents. Microscopy revealed the impairment of intestinal epithelial cells. High-throughput sequencing showed the Operational Taxonomic Units changed from 361 ± 33, 634 ± 18, 639 ± 19 in the normal jejunum, appendix, colon to 748 ± 98, 230 ± 11, 253 ± 16 in the disordered segments, respectively. In dysbiosis, Bacteroidetes translocated inversely from the colon and appendix (0.26%, 0.23%) to the jejunum (13.87% ± 0.11%); the relative abundance of all intestinal Enterococcaceae increased, while Lactobacillaceae decreased. Several bacterial clusters were found correlated to the normal appendix, whereas nonspecific clusters correlated to the disordered appendix. In conclusion, species richness and evenness reduced in the disordered appendix and colon; similar microbiome patterns were shared between the appendix and colon regardless of dysbiosis; site-specific bacteria were missing in the disordered appendix. Appendix is likely a transit region involving in upper and lower intestinal microflora modulation. The limitation of this study is all the data were derived from rats. We must be cautious about translating the microbiome results from rats to humans.

Looking for Possible Benefits of Combining Short-Chain Fructo-Oligosaccharides (scFOS) with Saccharomyces cerevisiae Sc 47 on Weaned Pigs Orally Challenged with Escherichia coli F4.

The objective of this work was to evaluate the effect of supplementing short-chain fructo-oligosaccharides (scFOS) combined or not with live yeast Saccharomyces cerevisiae Sc 47 on weanling pigs challenged with Escherichia coli F4+. We allocated ninety-six piglets to four experimental diets: control (CTR); supplemented with scFOS (5 g/kg Profeed® P95) (scFOS); S. cerevisiae Sc 47 (1 g/kg Actisaf® Sc 47 HR +) (YEA); or both (SYN). Parameters included: performance; E. coli F4+ detection; fermentation activity; inflammatory biomarkers; and ileal histomorphology. Our results showed that supplementing scFOS was able to reduce the incidence of diarrhea, and both supplements were able to lower counts of EHEC along the gut. Supplementing scFOS was mostly associated with changes in the gut ecosystem and increases in the lactobacilli population, while S. cerevisiae Sc 47 registered increases in the numbers of ileal intraepithelial lymphocytes. The synbiotic mixture showed the lowest diarrhea incidence and fecal scores, benefiting from complementary modes of action and possible synergistic effects due to a hypothesized yeast-LAB cross-feeding phenomenon in the foregut. In conclusion, our results evidence that supplementing scFOS or Saccharomyces cerevisiae Sc 47 is efficacious to fight post-weaning colibacillosis, and combining both could be beneficial in high-risk scenarios.

Exposure to polyethylene microplastics alters immature gut microbiome in an infant in vitro gut model.

Infants are characterized by an immaturity of the gut ecosystem and a high exposure to microplastics (MPs) through diet, dust and suckling. However, the bidirectional interactions between MPs and the immature infant intestinal microbiota remain unknown. Our study aims to investigate the impact of chronic exposure to polyethylene (PE) MPs on the gut microbiota and intestinal barrier of infants, using the new Toddler mucosal Artificial Colon coupled with a co-culture of epithelial and mucus-secreting cells. Gut microbiota composition was determined by 16S metabarcoding and microbial activities were evaluated by gas, short chain fatty acid and volatolomics analyses. Gut barrier integrity was assessed via evaluation of intestinal permeability, inflammation and mucus synthesis. Exposure to PE MPs induced gut microbial shifts increasing α-diversity and abundance of potentially harmful pathobionts, such as Dethiosulfovibrionaceae and Enterobacteriaceae. Those changes were associated to butyrate production decrease and major changes in volatile organic compounds profiles. In contrast, no significant impact of PE MPs on the gut barrier, as mediated by microbial metabolites, was reported. For the first time, this study indicates that ingestion of PE MPs can induce perturbations in the gut microbiome of infants. Next step would be to further investigate the potential vector effect of MPs.

Beyond bacteria: Reconstructing microorganism connections and deciphering the predicted mutualisms in mammalian gut metagenomes.

Numerous gut microbial studies have focused on bacteria. However, archaea, viruses, fungi, protists, and nematodes are also regular residents of the gut ecosystem. Little is known about the composition and potential interactions among these six kingdoms in the same samples. Here, we unraveled the complex connection among them using approximately 123 gut metagenomes from 42 mammalian species (including carnivores, omnivores, and herbivores). We observed high variation in bacterial and fungal families and relatively low variation in archaea, viruses, protists, and nematodes. We found that some fungi in the mammalian intestine might come from environmental sources (e.g., soil and dietary plants), and some might be native to the intestine (e.g., the occurrence of Neocallimastigomycetes). The Methanobacteriaceae and Plasmodiidae families (archaea and protozoa, respectively) were predominant in these metagenomes, whereas Onchocercidae and Trichuridae were the two most common nematodes, and Siphoviridae and Myoviridae the two most common virus families in these mammalian gut metagenomes. Interestingly, most of the pairwise co-occurrence patterns were significantly positive among these six kingdoms, and significantly negative networks mainly occurred between fungi and prokaryotes (both bacteria and archaea). Our study revealed some inconvenient characteristics in the mammalian gut microorganism ecosystem: (1) the community formed by members of the analyzed kingdoms reflects the life history of the host and the potential threat posed by pathogenic protists and nematodes in mammals; and (2) the networks suggest the existence of predicted mutualism among members of these six kingdoms and of the predicted competition, mainly among fungi and other kingdoms.

DOP50 Impact of Inflammatory Bowel Disease associated dysbiosis on bacterial quorum sensing mediated by Acyl-homoserine Lactone in human gut microbiota

Abstract Background Intestinal dysbiosis is a key feature in the pathogenesis of inflammatory bowel diseases (IBD). Bacterial quorum sensing mediated by acyl-homoserine lactones (AHL) might play a role in the dialogue between the gut microbiota and the host. The main objective of our study was to investigate the presence and expression of AHL synthase and receptor genes in the human gut ecosystem during IBD. Methods To confirm the presence of AHL in the gut, mass spectrometric detection was performed on stool samples from IBD patients and non-IBD subjects. Then, by an in silico approach, we exploited the open access database: Inflammatory Bowel Disease Multi’omics Database, an American cohort with bacterial metagenomes and metatranscriptomes data of stool samples from non-IBD and IBD subjects. To characterise gut dysbiosis, the most discriminating bacterial species between non-IBD and IBD patients were identified by multivariate analysis and allowed us to define two groups (dysbiosis/non-dysbiosis). The search for AHL synthase (luxI) and receptor (luxR) known homolog genes, was performed using Basic Local Alignment Search Tool (BLAST) from previously assembled gene files (presence/absence) as well as raw data sequencing files (relative abundance and expression). Results Mass spectrometry confirmed a higher concentration of AHL molecules in healthy subjects than in relapsing IBD. Regarding in silico analysis, 103 subjects were selected including 50 with Crohn’s disease (CD), 27 with ulcerative colitis (UC), and 26 non-IBD subjects. No luxI-like synthase genes were retrieved by BLAST searches. However, several homologs of receptor genes were identified: sdiA gene from Escherichia coli (7/103 patients) and luxR-like homologs from Bacteroides fragilis and Bacteroides dorei present in all patients. According to disease, only one luxR-like gene from Bacteroides dorei was under-expressed in IBD patients (p = 0.02) compared to non-IBD, especially in CD (p = 0.02) (Figure 1). In dysbiosis situation, one luxR receptor gene from Bacteroides fragilis appeared to be over-expressed (p = 0.04) compared to non-dysbiotic patients (Figure 2). Conclusion Through this computational approach, AHL-synthesising bacteria have not been found. However, the expression of quorum sensing receptor genes appears to be modulated by IBD-associated gut dysbiosis. The role of LuxR receptors, especially in Bacteroides species, should be investigated to understand its impact on gut microbiota (Figure 3). Targeting LuxR receptors of bacterial quorum sensing might represent a new approach to modulate the gut microbiota in IBD.

RGI-Type Pectic Polysaccharides Modulate Gut Microbiota in a Molecular Weight-Dependent Manner In Vitro.

In this study, the fermentation characteristics of high rhamnogalacturonan I pectic polysaccharides (RGI) and free-radical degraded RGI (DRGI) were evaluated by a human fecal batch-fermentation model, and their structural properties were also investigated. As a result, the Mw of RGI decreased from 246.8 to 11.6 kDa, and the branches were broken dramatically. Fermentation showed that RGI degraded faster and produced more acetate and propionate than DRGI. Both of them reduced the Firmicutes/Bacteroidetes ratio and promoted the development of Bacteroides, Bifidobacterium, and Lactobacillus, bringing benefits to the gut ecosystem. However, the composition and metabolic pathways of the microbiota in RGI and DRGI were different. Most of the dominant bacteria of RGI (such as [Eubacterium]_eligens_group) participated in carbohydrate utilization, leading to better performance in glucolipid metabolism and energy metabolism. This work elucidated that large molecular weight matters in the gut microbiota modulatory effect of RGI-type pectic polysaccharides in vitro.

Gut Microbial Perturbation and Host Response Induce Redox Pathway Upregulation along the Gut-Liver Axis during Giardiasis in C57BL/6J Mouse Model.

Apicomplexan infections, such as giardiasis and cryptosporidiosis, negatively impact a considerable proportion of human and commercial livestock populations. Despite this, the molecular mechanisms of disease, particularly the effect on the body beyond the gastrointestinal tract, are still poorly understood. To highlight host-parasite-microbiome biochemical interactions, we utilised integrated metabolomics-16S rRNA genomics and metabolomics-proteomics approaches in a C57BL/6J mouse model of giardiasis and compared these to Cryptosporidium and uropathogenic Escherichia coli (UPEC) infections. Comprehensive samples (faeces, blood, liver, and luminal contents from duodenum, jejunum, ileum, caecum and colon) were collected 10 days post infection and subjected to proteome and metabolome analysis by liquid and gas chromatography-mass spectrometry, respectively. Microbial populations in faeces and luminal washes were examined using 16S rRNA metagenomics. Proteome-metabolome analyses indicated that 12 and 16 key pathways were significantly altered in the gut and liver, respectively, during giardiasis with respect to other infections. Energy pathways including glycolysis and supporting pathways of glyoxylate and dicarboxylate metabolism, and the redox pathway of glutathione metabolism, were upregulated in small intestinal luminal contents and the liver during giardiasis. Metabolomics-16S rRNA genetics integration indicated that populations of three bacterial families-Autopobiaceae (Up), Desulfovibrionaceae (Up), and Akkermanasiaceae (Down)-were most significantly affected across the gut during giardiasis, causing upregulated glycolysis and short-chained fatty acid (SCFA) metabolism. In particular, the perturbed Akkermanasiaceae population seemed to cause oxidative stress responses along the gut-liver axis. Overall, the systems biology approach applied in this study highlighted that the effects of host-parasite-microbiome biochemical interactions extended beyond the gut ecosystem to the gut-liver axis. These findings form the first steps in a comprehensive comparison to ascertain the major molecular and biochemical contributors of host-parasite interactions and contribute towards the development of biomarker discovery and precision health solutions for apicomplexan infections.

Bacteroides vulgatus Ameliorates Lipid Metabolic Disorders and Modulates Gut Microbial Composition in Hyperlipidemic Rats.

Hyperlipidemia is a risk factor and key indicator for cardiovascular diseases, and the gut microbiota is highly associated with hyperlipidemia. Bacteroides vulgatus is a prevalent mutualist across human populations and confers multiple health benefits such as immunoregulation, antiobesity, and coronary artery disease intervention. However, its role in antihyperlipidemia has not been systematically characterized. This study sought to identify the effect of B. vulgatus Bv46 on hyperlipidemia. Hyperlipidemic rats were modeled by feeding them a high-fat diet for 6 weeks. The effect of B. vulgatus Bv46 supplementation was evaluated by measuring anthropometric parameters, lipid and inflammation markers, and the liver pathology. Multi-omics was used to explore the underlying mechanisms. The ability of B. vulgatus Bv46 to produce bile salt hydrolase was confirmed by gene annotation and in vitro experiments. Oral administration of B. vulgatus Bv46 in hyperlipidemic rats significantly reduced the body weight gain, food efficiency, and liver index, improved the serum lipid profile, lowered the levels of serum inflammatory cytokines, promoted the loss of fecal bile acids (BAs), and extended the fecal pool of short-chain fatty acids (SCFAs), especially propionate and butyrate. B. vulgatus Bv46 induced compositional shifts of the gut microbial community of hyperlipidemic rats, characterized by a lower ratio of Firmicutes to Bacteroidetes with an increase of genera Bacteroides and Parabacteroides. After intervention, serum metabolite profiling exhibited an adaptation in amino acids and glycerophospholipid metabolism. Transcriptomics further detected altered biological processes, including primary bile acid biosynthesis and fatty acid metabolic process. Taken together, the findings suggest that B. vulgatus Bv46 could be a promising candidate for interventions against hyperlipidemia. IMPORTANCE As a core microbe of the human gut ecosystem, Bacteroides vulgatus has been linked to multiple aspects of metabolic disorders in a collection of associative studies, which, while indicative, warrants more direct experimental evidence to verify. In this study, we experimentally demonstrated that oral administration of B. vulgatus Bv46 ameliorated the serum lipid profile and systemic inflammation of high-fat diet-induced hyperlipidemic rats in a microbiome-regulated manner, which appears to be associated with changes of bile acid metabolism, short-chain fatty acid biosynthesis, and serum metabolomic profile. This finding supports the causal contribution of B. vulgatus in host metabolism and helps to form the basis of novel therapies for the treatment of hyperlipidemia.

The eukaryome of African children is influenced by geographic location, gut biogeography, and nutritional status.

Eukaryotes have historically been studied as parasites, but recent evidence suggests they may be indicators of a healthy gut ecosystem. Here, we describe the eukaryome along the gastrointestinal tract of children aged 2-5 years and test for associations with clinical factors such as anaemia, intestinal inflammation, chronic undernutrition, and age. Children were enrolled from December 2016 to May 2018 in Bangui, Central African Republic and Antananarivo, Madagascar. We analyzed a total of 1104 samples representing 212 gastric, 187 duodenal, and 705 fecal samples using a metabarcoding approach targeting the full ITS2 region for fungi, and the V4 hypervariable region of the 18S rRNA gene for the overall eukaryome. Roughly, half of all fecal samples showed microeukaryotic reads. We find high intersubject variability, only a handful of taxa that are likely residents of the gastrointestinal tract, and frequent co-occurrence of eukaryotes within an individual. We also find that the eukaryome differs between the stomach, duodenum, and feces and is strongly influenced by country of origin. Our data show trends towards higher levels of Fusarium equiseti, a mycotoxin producing fungus, and lower levels of the protist Blastocystis in stunted children compared to nonstunted controls. Overall, the eukaryome is poorly correlated with clinical variables. Our study is of one of the largest cohorts analyzing the human intestinal eukaryome to date and the first to compare the eukaryome across different compartments of the gastrointestinal tract. Our results highlight the importance of studying populations across the world to uncover common features of the eukaryome in health.

Gastric Cancer: The Microbiome Beyond Helicobacter pylori.

Gastric cancer remains an important global health burden. Helicobacter pylori is the major etiological factor in gastric cancer, infecting the stomach of almost half of the population worldwide. Recent progress in microbiome research offered a new perspective on the complexity of the microbial communities of the stomach. Still, the role of the microbiome of the stomach beyond H. pylori in gastric carcinogenesis is not well understood and requires deeper investigation. The gastric bacterial communities of gastric cancer patients are distinct from those of patients without cancer, but the microbial alterations that occur along the process of gastric carcinogenesis, and the mechanisms through which microorganisms influence cancer progression still need to be clarified. Except for Epstein-Barr virus, the potential significance of the virome and of the mycobiome in gastric cancer have received less attention. This chapter updates the current knowledge regarding the gastric microbiome, including bacteria, viruses, and fungi, within the context of H. pylori-mediated carcinogenesis. It also reviews the possible roles of the local gastric microbiota, as well as the microbial communities of the oral and gut ecosystems, as biomarkers for gastric cancer detection. Finally, it discusses future perspectives and acknowledges limitations in the area of microbiome research in the gastric cancer setting, to which further research efforts should be directed. These will be fundamental not only to increase our current understanding of host-microbial interactions but also to facilitate translation of the findings into innovative preventive, diagnostic, and therapeutic strategies to decrease the global burden of gastric cancer.

Impacts of gut microbiota on human health and diseases

Numerous microorganisms that are important to the health of their host are found in abundance in the human gut. They can, however, also be potentially dangerous because of the alteration in their composition that occurs when the gut ecosystem experiences aberrant changes as a result of the use of antibiotics, sickness, stress, age, poor dietary practices, and lifestyle choices. Dysbiosis of the gut micro biota on humans has harmful health effects that can result in a number of chronic disorders. The potential of probiotics to treat certain disorders has led to much research into them. They are typically thought of as helpful microbes; additionally, when their products are supplied to humans in sufficient doses, they act as health adjuvants. Probiotics can prevent the beginning of disease through a number of processes, including altering gut bacteria, producing short-chain fatty acids, reducing intestinal pH, producing antimicrobial compounds, and suppressing epithelial binding growth. Additionally, they help to inhibit the invasion of pathogenic organisms, regulate the transfer of food antigens, enhance intestinal barrier performance, and alter host immunological responses. Probiotic tests have revealed encouraging outcomes in the prevention of diseases such as diarrhea, irritable bowel syndrome, colon cancer, and Crohn’s disease. Numerous epidemiological and experimental investigations, particularly those focusing on the gut microbiota, have contributed to shed light on the role of probiotics as preventative agents. This review provides a potential target for the illness prevention and treatment by summarizing and discussing the roles and potential mechanisms of gut bacteria in human health and disorders.

An insight into the commercial piglet’s microbial gut colonization: from birth towards weaning

BackgroundThe establishment of the gut microbiota can be influenced by several perinatal factors, including, most importantly, the maternal microbiota. Moreover, early-life environmental variation affects gut microbial colonization and the intestinal health of offspring throughout life. The present study aimed to explore the development of piglet gut microbiota from birth to weaning in the commercial practice and also to assess how different farm environments could condition this process. Although it is possible to find in the literature other studies with similar objectives this work probably represents one of the few studies that make a systematic evaluation of such differential factors under a real scenario. To achieve this objective, we performed two trials. In a first Trial, we selected 2 farms in which we performed an intensive sampling (5 samples /animal) to characterize the gut colonization pattern during the first days of life and to identify the time window with the greatest impact. Both farms differed in their health status and the use of antimicrobials in the piglets. In a second Trial, we selected 4 additional farms with variable rearing conditions and a distinctive use of antimicrobials in the sows with a simplified sampling pattern (2 samples/animal). Faecal samples were obtained with swabs and DNA was extracted by using the PSP® Spin Stool DNA Kit and sequencing of the 16S rRNA gene (V3-V4 region) performed by Illumina MiSeq Platform.ResultsThe present study contributes to a better understanding of microbiome development during the transition from birth to weaning in commercial conditions. Alpha diversity was strongly affected by age, with an increased richness of species through time. Beta diversity decreased after weaning, suggesting a convergent evolvement among individuals. We pinpointed the early intestinal colonizers belonging to Bacteroides, Escherichia-Shigella, Clostridium sensu stricto 1, and Fusobacterium genera. During lactation(d7-d21 of life), the higher relative abundances of Bacteroides and Lactobacillus genera were correlated with a milk-oriented microbiome. As the piglets aged and after weaning (d36 of life), increasing abundances of genera such as Prevotella, Butyricimonas, Christensenellaceae R-7 group, Dorea, Phascolarctobacterium, Rikenellaceae RC9 gut group, Subdoligranulum, and Ruminococcaceae UCG-002 were observed. These changes indicate the adaptation of the piglets to a cereal-based diet rich in oligosaccharides and starch. Our results also show that the farm can have a significant impact in such a process, evidencing the influence of different environments and rearing systems on the gut microbiota development of the young piglet. Differences between farms were more noticeable after weaning than during lactation with changes in alpha and beta biodiversity and specific taxa. The analysis of such differences suggests that piglets receiving intramuscular amoxicillin (days 2–5 of life) and being offered an acidifying rehydrating solution (Alpha farm in Trial 1) have a greater alpha diversity and more abundant Lactobacillus population. Moreover, the only farm that did not offer any rehydrating solution (Foxtrot farm in Trial 2) showed a lower alpha diversity (day 2 of life) and increased abundance of Enterobacteriaceae (both at 2 and 21 days). The use of in-feed antibiotics in the sows was also associated with structural changes in the piglets’ gut ecosystem although without changes in richness or diversity. Significant shifts could be registered in different microbial groups, particularly lower abundances of Fusobacterium in those piglets from medicated sows.ConclusionsIn conclusion, during the first weeks of life, the pig microbiota showed a relevant succession of microbial groups towards a more homogeneous and stable ecosystem better adapted to the solid dry feed. In this relevant early-age process, the rearing conditions, the farm environment, and particularly the antimicrobial use in piglets and mothers determine changes that could have a relevant impact on gut microbiota maturation. More research is needed to elucidate the relative impact of these farm-induced early life-long changes in the growing pig.

Impact of IBD-Associated Dysbiosis on Bacterial Quorum Sensing Mediated by Acyl-Homoserine Lactone in Human Gut Microbiota

Intestinal dysbiosis is a key feature in the pathogenesis of inflammatory bowel disease (IBD). Acyl-homoserine lactones (AHL) are bacterial quorum-sensing metabolites that may play a role in the changes in host cells-gut microbiota interaction observed during IBD. The objective of our study was to investigate the presence and expression of AHL synthases and receptor genes in the human gut ecosystem during IBD. We used an in silico approach, applied to the Inflammatory Bowel Disease Multi'omics Database comprising bacterial metagenomic and metatranscriptomic data from stools of patients with Crohn's disease (CD) (n = 50), ulcerative colitis (UC) (n = 27) and non-IBD controls (n = 26). No known putative AHL synthase gene was identified; however, several putative luxR receptors were observed. Regarding the expression of these receptor genes, the luxR gene from Bacteroides dorei was under-expressed in IBD patients (p = 0.02) compared to non-IBD patients, especially in CD patients (p = 0.02). In the dysbiosis situation, one luxR receptor gene from Bacteroides fragilis appeared to be over-expressed (p = 0.04) compared to that of non-dysbiotic patients. Targeting LuxR receptors of bacterial quorum sensing might represent a new approach to modulate the gut microbiota in IBD.

CONCOMITANT SOMATIC DISEASES IN CHILDREN WITH AUTISTIC SPECTRUM DISORDERS: CHALLENGING ISSUES OF MEDICAL OBSERVATION BY PEDIATRICIANS (LITERATURE REVIEW)

An analysis of modern medical literature carried out to study the main concomitant pathology in children with autism spectrum disorders gas revealed what concomitant diseases are more common in children with autism than in the general population. The structure of concomitant somatic pathology of children with autism includes disturbances from the gastrointestinal tract, sleep disturbances, the risk of overweight and obesity that affects the quality of life and complicates the manifestations of the main disease. The review of the current scientific literature has provided preliminary evidence that targeting the gut ecosystem has the potential to influence both autism spectrum disorders symptoms and gastrointestinal symptoms. The use of prebiotics and probiotics to correct behaviour and treat gastrointestinal diseases in children with autism has had limited effectiveness. The effectiveness and safety of using a gluten-free and casein-free diet in autism spectrum disorder is remaining controversial: a number of studies have reported no significant changes in autism symptoms, and the risk of developing nutrient deficiencies limits its clinical use. A combination of behavioural interventions and the use of the paediatric slow-release melatonin molecule are effective in the treatment of sleep disorders in children with autism.
 Conclusion. The high prevalence of concomitant somatic pathology in children with autism affects the course of the main disease, requiring a comprehensive examination of these children for its timely diagnosis and treatment. Taking into account the polyetiological nature of the etiopathogenetic mechanism of the development of autism spectrum disorder, the treatment of children with autism by a paediatrician should be carried out using evidence-based methods, with multidisciplinary support by specialists in the profile of existing concomitant disorders.