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Associations between gut microbiota on carcass traits and meat quality in Neijiang pigs, Yorkshire pigs, and their hybrids.

This study was designed as an exploratory analysis to compare carcass performance, meat quality traits, and gut microbiota of Neijiang pigs (NN), Yorkshire pigs (YY), and Yorkshire &#xd7; Neijiang hybrid pigs (YN), with the goal of generating testable hypotheses regarding potential links between gut microbial composition and production phenotypes. Compared with NN pigs, YN hybrids exhibited improved carcass performance while inheriting the favorable meat quality characteristics of Neijiang pigs. The results of 16S rRNA sequencing analysis showed that the relative abundance of the microbiota was similar to that of NN pigs. LDA effect size (LEfSe) results showed that Streptococcus, Treponema, probable_genus_10 and Fibrobacter were the differentially enriched taxa in YN pigs (p < 0.05). Correlation analysis was performed on carcass, meat quality and intestinal microbiota screened out by LEfSe. The results showed that Akkermansia tended to positively associate with body length and oblique length in YN pigs; Dialister correlated positively with dressing rate and pH45min; Treponema showed positive trends with a*45min and a*24h (p < 0.05). Finally, the correlation network model preliminarily mapped associations among production traits, gut microbiota, and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways for exploratory screening. Nine core microbial taxa exhibited close correlations with phenotypic indicators, which implied that these microbes might modulate metabolic pathways to shape pig performance. Overall, hybrids inherited superior parental carcass and meat quality but harbored unique gut microbial communities relative to purebreds-these preliminary correlative observations generate new hypotheses that gut microbiota may contribute to heterosis-associated phenotypic advantages, which require further targeted validation.

Animals↗

Functional genomic and metabolic studies of the adaptations of a prominent adult human gut symbiont, Bacteroides thetaiotaomicron, to the suckling period.

The adult human gut microbiota is dominated by two divisions of Bacteria, the Bacteroidetes and the Firmicutes. Assembly of this community begins at birth through processes that remain largely undefined. In this report, we examine the adaptations of Bacteroides thetaiotaomicron, a prominent member of the adult distal intestinal microbiota, during the suckling and weaning periods. Germ-free NMRI mice were colonized at birth from their gnotobiotic mothers, who harbored this anaerobic Gram-negative saccharolytic bacterium. B. thetaiotaomicron was then harvested from the ceca of these hosts during the suckling period (postnatal day 17) and after weaning (postnatal day 30). Whole genome transcriptional profiles were obtained at these two time points using custom B. thetaiotaomicron GeneChips. Transcriptome-based in silico reconstructions of bacterial metabolism and gas chromatography-mass spectrometry and biochemical assays of carbohydrate utilization in vivo indicated that in the suckling gut B. thetaiotaomicron prefers host-derived polysaccharides, as well as mono- and oligosaccharides present in mother's milk. After weaning, B. thetaiotaomicron expands its metabolism to exploit abundant, plant-derived dietary polysaccharides. The bacterium's responses to postnatal alterations in its nutrient landscape involve expression of gene clusters encoding environmental sensors, outer membrane proteins involved in binding and import of glycans, and glycoside hydrolases. These expression changes are interpreted in light of a phylogenetic analysis that revealed unique expansions of related polysaccharide utilization loci in three human alimentary tract-associated Bacteroidetes, expansions that likely reflect the evolutionary adaptations of these species to different nutrient niches.

Animals↗

Phylogenetic analysis of the human gut microbiota using 16S rDNA clone libraries and strictly anaerobic culture-based methods.

The human gut microbiota from three healthy subjects were compared by the use of a sequence analysis of 16S rDNA libraries and a culture-based method. Direct counts ranged from 1.9 X 10" to 4.0 X 10" cells/g (wet weight), and plate counts totaled 6.6 X 10(10) to 1.2 X 10(11) CFU/g (wet weight). Sixty to seventy percent of the bacteria in the human intestinal tract cannot be cultured with currently available methods. The 16S rDNA libraries from three subjects were generated from total community DNA in the intestinal tract with universal primer sets. Randomly selected clones were partially sequenced. All purified colonies detected from the surface of the agar plate were used for a partial sequencing of 16S rDNA. On the basis of sequence similarities, the clones and colonies were classified into several clusters corresponding to the major phylum of the domain Bacteria. Among a total of 744 clones obtained, approximately 25% of them belonged to 31 known species. About 75% of the remaining clones were novel "phylotypes" (at least 98% similarity of clone sequence). The predominant intestinal microbial community consisted of 130 species or phylotypes according to the sequence data in this study. The 16S rDNA libraries and colonies included the Bacteroides group, Streptococcus group, Bifidobacterium group, and Clostridium rRNA clusters IV, IX, XIVa, and XVIII. Moreover, several previously uncharacterized and uncultured microorganisms were recognized in clone libraries and colonies. Our results also showed marked individual differences in the composition of intestinal microbiota.

Adult↗

Polychlorinated biphenyl-degrading pseudomonads: survival in mouse intestines and competition with normal flora.

Although naturally occurring and mutant organisms, historically, have been released into the environment for various purposes, health concerns associated with the release of microorganisms have recently resurfaced. Federal agencies have been given the task of reassuring society that any released organisms are not likely to produce adverse health effects. Methods, therefore, for evaluating the potential health effects due to environmental release of mutant and genetically engineered microorganisms are under investigation. A mouse model was developed that examines morbidity, mortality, and more indirect effects such as colonization potential of the intestinal tract, as well as competition with and alteration of the intestinal microbiota populations. The Pseudomonas spp. used in this study were isolated from a commercial product and used for degrading polychlorinated biphenyls. Mice were dosed individually with 10(3), 10(6), and 10(9) colony-forming units of each microorganism. At specific time intervals the intestines were removed and examined for the presence of the dosed microorganism. At the two higher doses, 10(6) and 10(9) colony-forming units, P. maltophilia strain BC6 and two P. aeruginosa strains, BC16 and BC18, were recoverable 48 h after dosing. The naturally occurring P. aeruginosa strain, PAMG, isolated from a mouse intestinal homogenate produced a similar response. Statistical analysis indicated that in some of the dosed animals, an alteration in the distribution of normal intestinal microflora occurred. Pseudomonas maltophilia strain BC6 and P. aeruginosa strains BC16 and BC17 caused a change in the obligately anaerobic predominantly gram-negative rod counts, and P. aeruginosa strain BC17 produced a dose effect on the total anaerobic count at the 10% confidence level. The total aerobic count was unaffected by the presence of the dosed pseudomonads.

Animals↗

Use of denaturing gradient gel electrophoresis for analysis of the stool microbiota of hospitalized patients.

Denaturing gradient gel electrophoresis (DGGE) of PCR-amplified ribosomal RNA gene amplicons was used to study the stool microbiota of hospitalized patients and to examine the effect of antibiotic therapy. For one patient, 16 anaerobic species identified by random cloning and sequencing of PCR-amplified rRNA genes from stool were represented by bands on the DGGE gel. DGGE analysis and similarity index comparisons demonstrated that the anaerobic microbiota of this individual remained stable in the absence of antibiotic therapy, was minimally affected by ciprofloxacin but markedly reduced by clindamycin therapy, and recovery of some organisms was evident within days after discontinuation of clindamycin. DGGE analysis of additional patients demonstrated similar disruptions of the intestinal microbiota associated with antibiotic therapy. The DGGE banding patterns of nine patients showed considerable variability, but several bands were shared among patients. Thus, our findings are consistent with previous studies that utilized culture techniques, and suggest that DGGE is a useful technique for analysis of the stool microbiota of hospitalized patients.

Actinobacteria↗

Intestinal bacterial community and growth performance of chickens fed diets containing antibiotics.

This study was conducted to relate the performance of broiler chickens fed diets containing growth-promoting antibiotics to changes in the intestinal microbiota. The technique of denaturing gradient gel electrophoresis (DGGE) of amplicons of the region V3 of 16S rDNA was used to characterize the microbiota. Two experiments were conducted, one with broilers raised in battery cages and the other with broilers raised in floor pens. Antibiotics improved the performance of the chickens raised in floor pens only. Avilamycin, bacitracin methylene disalicylate, and enramycin induced changes in the composition of the intestinal bacterial community of the birds in both experiments. The number of bacterial genotypes found in the intestinal tract of chickens was not reduced by the antibiotics supplemented in either environment. However, the changes in the composition of the intestinal bacterial community induced by antibiotics may be related to improvement in growth performance. This was indicated by the suppression of 6 amplicons and the presence of 4 amplicons exclusive to the treatment that had the best performance in the floor pen experiment.

Animal Feed↗

Honor thy symbionts.

Our intestine is the site of an extraordinarily complex and dynamic environmentally transmitted consortial symbiosis. The molecular foundations of beneficial symbiotic host-bacterial relationships in the gut are being revealed in part from studies of simplified models of this ecosystem, where germ-free mice are colonized with specified members of the microbial community, and in part from comparisons of the genomes of members of the intestinal microbiota. The results emphasize the contributions of symbionts to postnatal gut development and host physiology, as well as the remarkable strategies these microorganisms have evolved to sustain their alliances. These points are illustrated by the human-Bacteroides thetaiotaomicron symbiosis. Interdisciplinary studies of the effects of the intestinal environment on genome structure and function should provide important new insights about how microbes and humans have coevolved mutually beneficial relationships and new perspectives about the foundations of our health.

Animals↗

Safety evaluation of Lactobacillus delbrueckii subsp. lactis UO 004, a probiotic bacterium.

Lactobacillus delbrueckii subsp. lactis UO 004 was evaluated for its use as a potential probiotic from a safety point of view. The strain did not exhibit mucinolytic or other enzymatic activities that might be detrimental, such as those involving glycosidases (beta-D-glucosaminidase or alpha-D-galactosidase) or arylamidases (factor Xa and quimotrypsin-like activities), frequently present in Lactobacillus strains isolated from patients with endocarditis, although it was able to express protein Ca and kallikrein-like activities. On the other hand, the presence of the strain did not interfere with the growth of certain species of normal intestinal microbiota, such as Enterococcus fecalis, Escherichia coli, Bifidobacterium bifidum or Bacteroides fragilis. Moreover, the potential probiotic strain UO 004 is sensitive to antibiotics with transmissible resistance mechanisms in Lactobacillus such as chloramphenicol, erythromycin, tetracycline and vancomycin. In addition, strain L. delbrueckii UO 004 was not able to translocate towards the intestinal barrier of mice or produce changes in their activity or general health status.

Animals↗

Identification of bacterial isolates obtained from intestinal contents associated with 12,000-year-old mastodon remains.

Mastodon (Mammut americanum) remains unearthed during excavation of ancient sediments usually consist only of skeletal material, due to postmortem decomposition of soft tissues by microorganisms. Two recent excavations of skeletal remains in anoxic sediments in Ohio and Michigan, however, have uncovered organic masses which appear to be remnants of the small and large intestines, respectively. Macrobotanical examinations of the composition of these masses revealed assemblages of plant material radiocarbon dated to approximately 11,500 years before the present and thought to be incompletely digested food remains from this extinct mammal. We attempted to cultivate and identify bacteria from the intestinal contents, bone-associated sediments, and sediments not in proximity to the remains using a variety of general and selective media. In all, 295 isolates were cultivated, and 38 individual taxa were identified by fatty acid-methyl ester (FAME) profiles and biochemical characteristics (API-20E). The taxonomic positions of selected enteric and obligately anaerobic bacteria were confirmed by 16S ribosomal DNA (rDNA) sequencing. Results indicate that the intestinal and bone-associated samples contained the greatest diversity of bacterial taxa and that members of the family Enterobacteriaceae represented 41% of all isolates and were predominant in the intestinal masses and sediments in proximity to the skeleton but were uncommon in the background sediments. Enterobacter cloacae was the most commonly identified isolate, and partial rDNA sequencing revealed that Rahnella aquatilis was the correct identity of strains suggested by FAME profiles to be Yersinia enterocolitica. No Bacteroides spp. or expected intestinal anaerobes were recovered. The only obligate anaerobes recovered were clostridia, and these were not recovered from the small intestinal masses. Microbiological evidence from this study supports other, macrobotanical data indicating the intestinal origin of these masses. Whether these organisms are direct descendants of the original intestinal microbiota, however, cannot be established.

Animals↗

Monoassociation with Lactobacillus acidophilus UFV-H2b20 stimulates the immune defense mechanisms of germfree mice.

Probiotics are formulations containing live microorganisms or microbial stimulants that have some beneficial influence on the maintenance of a balanced intestinal microbiota and on the resistance to infections. The search for probiotics to be used in prevention or treatment of enteric infections, as an alternative to antibiotic therapy, has gained significant impulse in the last few years. Several studies have demonstrated the beneficial effects of lactic acid bacteria in controlling infection by intestinal pathogens and in boosting the host's nonspecific immune response. Here, we studied the use of Lactobacillus acidophilus UFV-H2b20, a lactic acid bacterium isolated from a human newborn from Viçosa, Minas Gerais, Brazil, as a probiotic. A suspension containing 10(8) cells of Lactobacillus acidophilus UFV-H2b20 was inoculated into groups of at least five conventional and germfree Swiss mice to determine its capacity to stimulate the host mononuclear phagocytic activity. We demonstrate that this strain can survive the stressing conditions of the intestinal tract in vivo. Moreover, the monoassociation of germfree mice with this strain for seven days improved the host's macrophage phagocytic capacity, as demonstrated by the clearance of a Gram-negative bacterium inoculated intravenously. Monoassociated mice showed an undetectable number of circulating E. coli, while 0.1% of the original inoculum was still present in germfree animals. Mice treated with viable or heat-killed Lactobacillus acidophilus UFV-H2b20 presented similarly improved clearance capacity when compared with germfree controls. In addition, monoassociated mice had twice the amount of Kupffer cells, which are responsible for the clearance of circulating bacteria, compared to germfree controls. These results suggest that the L. acidophilus strain used here stimulates a nonspecific immune response and is a strong candidate to be used as a probiotic.

Animals↗

Role of bacterial colonization in neonatal necrotizing enterocolitis and its prevention.

Necrotizing enterocolitis (NEC) is the most common gastrointestinal emergency in premature infants. A major component of the pathophysiology of NEC is the nature of the interaction of bacteria with the premature gut. Intestine microflora are important to the host in resistance to bacterial infections. Diet and environmental conditions can influence this ecosystem. A breast-fed full-term infant has a preferred intestine microbiota in which bifidobacteria predominate over the potentially harmful bacteria, whereas in formula-fed infants coliforms, enterococci and bacteroides predominate. The pattern of bacterial colonization in the premature neonate gut is quite different from that in the gut of the healthy full-term infant. Those infants requiring intensive care acquire intestinal organisms slowly, and the establishment of bifidobacterial flora is retarded. A delayed bacterial colonization of the gut with a limited number of bacterial species tends to be virulent. Bacterial overgrowth is one of major factors promoting bacterial translocation. The aberrant colonization of the premature infant may contribute to the development of NEC. Breast feeding protects infants against NEC. Oligosaccharides and glycoconjugates, natural components in human milk, may prevent intestinal attachment of enteropathogens by acting as receptor homologues. Probiotics and prebiotics modulate the composition of human intestine microflora to the benefit of the host. The beneficial effects may result in the suppression of colonization of harmful microoganisms and/or the stimulation of bifidobacterial growth. In the future, control and manipulation of bacterial colonization in the neonate gut may be a new approach to the prevention and treatment of bacterial intestinal disease of various etiologies.

Bacteria↗

The effects of dietary ferric iron and iron deprivation on the bacterial composition of the mouse intestine.

The influence of dietary ferric iron on the intestinal microbiota of mice was investigated with a view to promoting benign lactic acid bacteria (which have minimal iron requirements) in order to enhance colonization-resistance potential. Three groups of eight mice received a diet differing only in iron content, for a period of 12 weeks. Dietary iron deprivation resulted in overall increased small intestinal bacterial populations, including lactic acid bacteria, but these differences were generally not significant (p > 0.05). With the exception of coliforms, all examined bacterial groups (anaerobes, micro-aerophiles, lactobacilli, and enterococci) were significantly (p < 0.05) elevated in the colons of iron-deprived mice. The relatively low numbers of total anaerobes in the colons of iron-replete and iron-overloaded mice suggested that, as well as promotion of bacteria under iron-deprived condition, provision of ferric iron suppressed bacteria, probably by oxidation of normally reduced environments.

Animals↗

Determination of Vibrio scophthalmi and its phenotypic diversity in turbot larvae.

The association of Vibrio scophthalmi with turbot larvae was assessed, by molecular methods with a species-specific probe, in the rearing stages of turbot (Scophthalmus maximus) larvae using a routine batch of production at a fish farm. The phenotypic diversity of this bacterial species was also studied to identify predominant phenotypes at successive stages of larval development. Vibrio scophthalmi was detected in all turbot larvae samples except in the sample from day 0 after hatching. The percentage of V. scophthalmi in the intestinal microbiota increased throughout larval development. Vibrio scophthalmi was also detected in live food (brine shrimps) and water from the tanks, but not in the sediment. All turbot larvae, 15-57 day old, showed several V. scophthalmi phenotypes, and a pattern of successive waves of phenotypes was observed during successive larval stages. This indicates that certain strains may colonize the intestine more efficiently and thus maintain their population for longer than other strains. Vibrio scophthalmi populations from turbots of different origin were very similar, suggesting that irrespective of geographical area, turbot populations share similar V. scophthalmi strains. Vibrio scophthalmi strain was not isolated from other cultured fish, only turbot larvae, at the same hatchery receiving water from the same supply.

Animals↗

Specific probiotic therapy attenuates antibiotic induced visceral hypersensitivity in mice.

BACKGROUND AND AIMS: Abdominal pain and discomfort are common symptoms in functional disorders and are attributed to visceral hypersensitivity. These symptoms fluctuate over time but the basis for this is unknown. Here we examine the impact of changes in gut flora and gut inflammatory cell activity on visceral sensitivity. METHODS: Visceral sensitivity to colorectal distension (CRD) was assessed at intervals in healthy mice for up to 12 weeks, and in mice before and after administration of dexamethasone or non-absorbable antibiotics with or without supplementation with Lactobacillus paracasei (NCC2461). Tissue was obtained for measurement of myeloperoxidase activity (MPO), histology, microbiota analysis, and substance P (SP) immunolabelling. RESULTS: Visceral hypersensitivity developed over time in healthy mice maintained without sterile precautions. This was accompanied by a small increase in MPO activity. Dexamethasone treatment normalised MPO and CRD responses. Antibiotic treatment perturbed gut flora, increased MPO and SP immunoreactivity in the colon, and produced visceral hypersensitivity. Administration of Lactobacillus paracasei in spent culture medium normalised visceral sensitivity and SP immunolabelling, but not intestinal microbiota counts. CONCLUSION: Perturbations in gut flora and in inflammatory cell activity alter sensory neurotransmitter content in the colon, and result in altered visceral perception. Changes in gut flora may be a basis for the variability of abdominal symptoms observed in functional gastrointestinal disorders and may be prevented by specific probiotic administration.

Abdominal Pain↗

Effects of aerobic exercise on inflammation and gut microbiota in obese mice: a metagenomic and metabolomic analysis.

BACKGROUND: Aerobic exercise can ameliorate insulin resistance (IR). However, the mechanism by which aerobic exercise regulates the gut microbiome to ameliorate IR and obesity remains unexplored. METHODS: Obese models were established by feeding C57BL/6 male mice a high-fat diet. A total of 26 mice were randomly divided into control group (group A, N&#x2009;=&#x2009;8) and high-fat diet group (HFD group, N&#x2009;=&#x2009;18). Successfully modeled mice were further assigned to model group (group B, N&#x2009;=&#x2009;8) and exercise group (group C, N&#x2009;=&#x2009;8). Group C underwent a 6-week treadmill exercise program (12&#xa0;m/min, 60&#xa0;min per day, 5 days per week). After intervention, colon tissue morphology was observed through hematoxylin-eosin staining, serum lipids and inflammatory indicators levels were detected by ELISA. The changes in the intestinal microbiota of the mice were also examined using metagenomic sequencing and UPLC-MS non-targeted metabolomics. RESULTS: Compared with the group A, the body weight, TC, TG, LDL-C, blood glucose, insulin, and IR in the group B significantly increased (P&#x2009;<&#x2009;0.01), while the levels of pro-inflammatory cytokines TXNIP, TNF-&#x3b1;, NLRP3, IL-1&#x3b2;, and IL-18 significantly increased (P&#x2009;<&#x2009;0.05 or P&#x2009;<&#x2009;0.01). Compared with the group B, aerobic exercise reduced the body weight, TC, blood glucose, insulin, IR, TXNIP, TNF-&#x3b1; and other indicators in obese mice (P&#x2009;<&#x2009;0.05 or P&#x2009;<&#x2009;0.01). Moreover, aerobic exercise can regulate the imbalance of the intestinal flora in obese mice and ameliorate the disorder of metabolites. The metabolic pathways including arachidonic acid metabolism and histidine metabolism showed the most significant differences after the intervention of aerobic exercise. CONCLUSIONS: In conclusion, aerobic exercise can ameliorate glucose and lipid metabolism, IR, inflammatory response, and regulate the intestinal microecology and metabolic disorders in obese mice. The mechanism may be closely related to enhancing the diversity of intestinal flora, regulating the metabolism of arachidonic acid and histidine.

Animals↗

Investigations of bifidobacterial ecology and oligosaccharide metabolism in a three-stage compound continuous culture system.

BACKGROUND: Several different types of in vitro fermentation systems are currently employed to investigate pro- and prebiotic activities in the human large intestinal microbiota, ranging from simple batch cultures, with or without stirring and pH control, to more complex models involving pH controlled single and multiple-component continuous culture systems. METHODS: In this investigation, we used a three-stage continuous culture model to study the activities of colonic bacteria. This fermentation system reproduces several of the nutritional and environmental characteristics of the proximal large intestine (vessel 1) and the distal colon (vessels 2 and 3), and was validated using bacteriological, metabolic and chemical measurements made with intestinal material obtained from different regions of the large bowel. In this paper, we report studies on prospective probiotic effects of Bifidobacterium longum NCFB 2259 in relation to other bacterial populations, production of tyrosine and phenylalanine metabolites, and bacterial synthesis of enzymes involved in the formation of putatively genotoxic metabolites, including beta-glucosidase (GS), arylsulphatase (AS), beta-glucuronidase (GN), nitroreductase (NR) and azoreductase (AR). RESULTS: Bacterial activities at two different retention times were studied (31.1 and 68.4 h), which correspond to large intestinal transit times. At R = 31.4 h, significant probiotic effects were observed with respect to reductions in GS and GN, upon adding B. longum. However, despite the fact that this organism does not ferment aromatic amino acids or produce significant amounts of genotoxic enzymes, dysbiotic manifestations occurred in that both NR synthesis and dissimilatory tyrosine metabolism were stimulated. In contrast, at R = 68.4 h, GS formation increased between five and 20-fold, while GN and NR activities increased by a factor of two after adding the bifidobacterium. These data are reviewed in relation to potential health hazards that may be encountered with long-term probiotic administration. In the prebiotic experiments, the three-stage fermentation system was operated at R = 65 h. Oligofructose was added to V1 to give an initial concentration of 30 grams per litre, when the system was in steady state, to study its effects on a number of experimental parameters including bifidogenicity, bacterial growth, fermentation product formation and mutagenicity. After addition of the oligosaccharide, a multiplicity of effects were observed in V1, where synthesis of NR and AR, bifidobacterial populations and overall fermentation processes were stimulated, although these influences progressively diminished in V2 and V3. CONCLUSIONS: These studies indicate that bacterial metabolism and putative beneficial consequences associated with the breakdown of readily fermentable prebiotics in the large intestine may in some circumstances be spatially and temporally limited to the proximal bowel.

Arylsulfatases↗

A genomic view of the human-Bacteroides thetaiotaomicron symbiosis.

The human gut is colonized with a vast community of indigenous microorganisms that help shape our biology. Here, we present the complete genome sequence of the Gram-negative anaerobe Bacteroides thetaiotaomicron, a dominant member of our normal distal intestinal microbiota. Its 4779-member proteome includes an elaborate apparatus for acquiring and hydrolyzing otherwise indigestible dietary polysaccharides and an associated environment-sensing system consisting of a large repertoire of extracytoplasmic function sigma factors and one- and two-component signal transduction systems. These and other expanded paralogous groups shed light on the molecular mechanisms underlying symbiotic host-bacterial relationships in our intestine.

Adult↗

Nucleotide-binding-oligomerization domain proteins and toll-like receptors: sensors of the inflammatory bowel diseases' microbial environment.

PURPOSE OF REVIEW: Chronic inflammatory bowel diseases appear to result from inappropriate immune responses driven by apparently normal intestinal microflora in genetically susceptible hosts. This review focuses on recently described mechanisms balancing toll-like receptor and nucleotide-binding-oligomerization domain activation in the face of ubiquitous enteric flora. RECENT FINDINGS: Toll-like receptor and nucleotide-binding-oligomerization domain signaling plays an integral role in the close collaboration between the intestinal epithelial cell monolayer and adjacent mucosal immune cells. Pathways activated by functional cytosolic nucleotide-binding-oligomerization domain proteins appear to interact with those mediated by membrane-associated toll-like receptors in the innate and adaptive immune defense against intra-and extracellular pathogens. Nucleotide-binding-oligomerization domain-mediated signaling may also control toll-like receptor-induced proinflammatory pathways. SUMMARY: Intersections between toll-like receptor and nucleotide-binding-oligomerization domain pathways may exist to refine the host immune response to pathogens and prevent undesired immune stimulation driven by the intestinal microbiota. Deficient toll-like receptor and nucleotide-binding-oligomerization domain function due to genetic variability is associated with an increased susceptibility to the development of inflammatory bowel disease.

Bacteria↗