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PubMed1992

Use of norfloxacin to study colonization ability of Escherichia coli in in vivo and in vitro models of the porcine gut.

The colonization resistance conveyed by the intestinal microbiota can prevent colonization of the intestinal system by new strains. In this study, this resistance was partly circumvented by use of the antimicrobial drug norfloxacin. The colonization abilities of two closely related Escherichia coli strains, which were resistant to nalidixic acid and rifampin, respectively, were investigated in minipigs and a two-stage continuous-flow in vitro gut model. Whereas both strains were unable to colonize the intact enteric system in vivo and in vitro, a 3-day norfloxacin treatment modified both systems to allow colonization by the nalidixic acid-resistant strain but not the rifampin-resistant strain. The results indicate the usefulness of norfloxacin to circumvent the normal colonization resistance while keeping a fairly normal microbiota in the gut. The results also indicate that it could be possible to construct in vitro gut models which could distinguish between strains with different gut colonization abilities. Both of these possibilities could come to be used in the study of the colonization and effects in the gut of new bacterial strains, i.e., genetically modified microorganisms.

Animals↗

PubMed2025

The role of mobile genetic elements in adaptation of the microbiota to the dynamic human gut ecosystem.

The human intestinal microbiota is a dynamic ecosystem shaped by extensive horizontal gene transfer, particularly in individuals from industrialized populations. In this review, we discuss recent advances in our understanding of how mobile genetic elements (MGEs) contribute to microbial ecology and evolution in this diverse community, focusing on MGEs carrying fitness-conferring genes. Bacteroidales species can colonize individuals for decades and serve as major hubs for MGE exchange. Most MGEs are highly variable across individuals and geographies. Occasionally, conserved MGEs can spread across geography and lifestyles. Functional characterizations of MGEs reveal their roles in antibiotic resistance, interbacterial antagonism, biofilm formation, immune evasion, and nutrient acquisition, among others. Substantive progress in our understanding of MGEs in the gut microbiome offers promising avenues for therapeutic microbiome interventions. However, major challenges remain in functional prediction, host-MGE linkage, and experimental characterization.

Humans↗

PubMed2006

Oligosaccharides isolated from goat milk reduce intestinal inflammation in a rat model of dextran sodium sulfate-induced colitis.

BACKGROUND AND AIMS: There is increased interest in the study of manipulation of the flora with pro- and prebiotics regarding inflammatory bowel disease. The aim of this work was to evaluate the effect of oligosaccharides from goat milk in a rat model of dextran sodium sulfate- (DSS-) induced colitis. METHODS: Twenty rats were fed the same diet but with different sources of fiber (5% of the diet): cellulose or a mixture of goat's milk oligosaccharides (GMO) and cellulose. DSS treatment was used to induce a colonic inflammation. Several clinical and inflammatory parameters, as well as intestinal micorbiota and gene expression by DNA microarray technology, were evaluated. RESULTS: DSS induced a decrease in body weight which was not observed in rats fed the GMO (decrease of 21+/-11% in control rats vs increase of 5.2+/-8.6 in GMO rats, P<0.05). DSS also caused an acute colonic inflammatory process which was weaker in rats fed the GMO, as shown by colon myeloperoxidase activity (0.53+/-0.16 vs 0.14+/-0.07U/mg of protein, P<0.05), as well as clinical symptoms measured by a scoring system (1.25+/-1.14 vs 0.4+/-0.07, P<0.05). GMO rats also showed less severe colonic lesions and a more favorable intestinal microbiota. The expression of genes involved in intestinal function, such as mucine-3, was down-regulated in DSS-control rats but returned to normal values in GMO rats. CONCLUSION: GMO reduce intestinal inflammation and contribute to the recovery of damaged colonic mucosa.

Animals↗

PubMedDate not supplied

Influence of high-calorie (cafeteria) diets on the population of Paneth cells in the small intestine of the rat.

A high-calorie (cafeteria) diet is known to cause changes in the intestinal morphology and functioning that seem to be related to calorie overfeeding. Among the cell lineages found in the small intestine epithelium, the Paneth cell (PC) population is known to be influenced by factors related mainly to the intestinal microbiota. The role of PCs in the intestinal cell concert remains unclear, because experimental evidence suggests PC involvement in local processes other than protection against pathogens. Participation of PC in digestive mechanisms has been proposed on this basis. We have analyzed the effect of high-carbohydrate (HC) and high-fat (HF) cafeteria diets on the PC population in the small intestine of the adult rat. For 8 weeks, both HC and HF diets caused a gain in body weight, but whereas the HC-fed rats showed reduced counts of intestinal crypts per 5-mum section, the HF-fed group showed the opposite. In control rats, the number of crypts per section showed a slight tendency to decrease along the duodenum - ileum axis, whereas the number of PCs per crypt was increased towards the ileum. As a result, the number of PCs per section (calculated from these data) remained constant along the three segments of the intestine. The hypercaloric diets did not modify the general tendencies seen in the crypt and PC counts, but reduced the number of PCs per section in the duodenum by 50%. HC-fed, but not HF-fed, rats showed a similar reduction in jejunum also. These changes do not correlate particularly with any of the predictable effects of diet composition, so that a multifactorial control of PC density is proposed.

Adipose Tissue↗

PubMed2002

The development of gut immune responses and gut microbiota: effects of probiotics in prevention and treatment of allergic disease.

The infant's immature intestinal immune system develops as it comes into contact with dietary and microbial antigens in the gut. The evolving indigenous intestinal microbiota have a significant impact on the developing immune system and there is accumulating evidence indicating that an intimate interaction between gut microbiota and host defence mechanisms is mandatory for the development and maintenance of a balance between tolerance to innocuous antigens and capability of mounting an inflammatory response towards potential pathogens. Disturbances in the mucosal immune system are reflected in the composition of the gut microbiota and vice versa. Distinctive alterations in the composition of the gut microbiota appear to precede the manifestation of atopic disease, which suggests a role for the interaction between the intestinal immune system and specific strains of the microbiota in the pathogenesis of allergic disorders. The administration of probiotics, strains of bacteria from the healthy human gut microbiota, have been shown to stimulate antiinflammatory, tolerogenic immune responses, the lack of which has been implied in the development of atopic disorders. Thus probiotics may prove beneficial in the prevention and alleviation of allergic disease.

Food Hypersensitivity↗

PubMed2004

Microbiota composition of the intestinal mucosa: association with fecal microbiota?

The fecal and mucosal microbiota of infants with rectal bleeding and the fecal microbiota of healthy age-matched controls were investigated by fluorescent in situ hybridization. Bifidobacteria were the main genus in both the feces and mucosa. The other genera tested, Bacteroides, Clostridium, Escherichia coli and lactobacilli/enterococci, represented only minor constituents. No differences in fecal microbiota were observed between patients and controls. In the patients, however, four times greater numbers of bifidobacteria were observed in the feces when compared to the mucosa. Notwithstanding this difference, a strong positive correlation prevailed for bifidobacteria in feces and mucosal samples. The genera assessed accounted for 16% of total bacterial counts on mucosal samples and for 47% of total bacterial counts in feces. This indicates that the unidentified part of the microbiota, especially on the mucosa, deserves more attention.

Bacteria↗

PubMed2005

Comparison between cultured small-intestinal and fecal microbiotas in beagle dogs.

The microbiota of the small intestine is poorly known because of difficulties in sampling. In this study, we examined whether the organisms cultured from the jejunum and feces resemble each other. Small-intestinal fluid samples were collected from 22 beagle dogs with a permanent jejunal fistula in parallel with fecal samples. In addition, corresponding samples from seven of the dogs were collected during a 4-week period (days 4, 10, 14, and 28) to examine the stability of the microbiota. In the jejunal samples, aerobic/facultative and anaerobic bacteria were equally represented, whereas anaerobes dominated in the fecal samples. Despite lower numbers of bacteria in the jejunum (range, 10(2) to 10(6) CFU/g) than in feces (range, 10(8) to 10(11) CFU/g), some microbial groups were more prevalent in the small intestine: staphylococci, 64% versus 36%; nonfermentative gram-negative rods, 27% versus 9%; and yeasts, 27% versus 5%, respectively. In contrast, part of the fecal dominant microbiota (bile-resistant Bacteroides spp., Clostridium hiranonis-like organisms, and lactobacilli) was practically absent in the jejunum. Many species were seldom isolated simultaneously from both sample types, regardless of their overall prevalence. In conclusion, the small intestine contains a few bacterial species at a time with vastly fluctuating counts, opposite to the results obtained for the colon, where the major bacterial groups remain relatively constant over time. Qualitative and quantitative differences between the corresponding jejunal and fecal samples indicate the inability of fecal samples to represent the microbiotas present in the upper gut.

Animals↗

PubMed2002

Antibiotics as growth promotants: mode of action.

Recent concerns about the use of growth-promoting antibiotics in pig diets have renewed interest in the immunologic and growth-regulating functions of the gastrointestinal (GI) tract. The numerically dense and metabolically active microbiota ofthe pig GI tract represents a key focal point for such questions. The intestinal microbiota is viewed typically as a beneficial entity for the host. Intestinal bacteria provide both nutritional and defensive functions for their host. However, the host animal invests substantially in defensive efforts to first sequester gut microbes away from the epithelial surface, and second to quickly mount immune responses against those organisms that breach epithelial defenses. The impact of host responses to gut bacteria and their metabolic activities require special consideration when viewed in the context of pig production in which efficiency of animal growth is a primary objective. Here, we summarize the working hypothesis that antibiotics improve the efficiency of animal growth via their inhibition of the normal microbiota, leading to increased nutrient utilization and a reduction in the maintenance costs ofthe GI system. In addition, novel molecular ecology techniques are described that can serve as tools to uncover the relationship between intestinal microbiology and growth efficiency.

Animal Feed↗

PubMed2007

Mechanisms of action of probiotics in intestinal diseases.

Intestinal microbiota is a positive health asset that exerts a conditioning effect on intestinal homeostasis. Resident bacteria deliver regulatory signals to the epithelium and instruct mucosal immune responses. Recent research has revealed a potential therapeutic role for the manipulation of the microbiota and exploitation of host-microbial signalling pathways in the maintenance of human health and treatment of various mucosal disorders. A variety of pharmabiotic strategies, such as the use of specific members of the microbiota, their surface components, or metabolites, as well as genetically modified commensal bacteria, are being investigated for their ability to enhance the beneficial components of the microbiota. It is clear that engagement with host cells is central to pharmabiotic action, and several strain-specific mechanisms of action have been elucidated. However, the molecular details underpinning these mechanisms remain almost entirely unknown. Understanding how pharmabiotics exert their beneficial effects is critical for the establishment of definitive selection criteria for certain pharmabiotic strategies for specific clinical conditions. Scientifically accredited evidence of efficacy and studies to elucidate the molecular mechanisms of host-microbiota interactions are needed to lend credence to the use of pharmabiotic strategies in clinical medicine.

Animals↗

PubMed2006

Dietary carbohydrate source influences molecular fingerprints of the rat faecal microbiota.

BACKGROUND: A study was designed to elucidate effects of selected carbohydrates on composition and activity of the intestinal microbiota. Five groups of eight rats were fed a western type diet containing cornstarch (reference group), sucrose, potato starch, inulin (a long- chained fructan) or oligofructose (a short-chained fructan). Fructans are, opposite sucrose and starches, not digestible by mammalian gut enzymes, but are known to be fermentable by specific bacteria in the large intestine. RESULTS: Animals fed with diets containing potato starch, or either of the fructans had a significantly (p < 0.05) higher caecal weight and lower caecal pH when compared to the reference group, indicating increased fermentation. Selective cultivation from faeces revealed a higher amount of lactic acid bacteria cultivable on Rogosa agar in these animals. Additionally, the fructan groups had a lower amount of coliform bacteria in faeces. In the inulin and oligofructose groups, higher levels of butyrate and propionate, respectively, were measured.Principal Component Analysis of profiles of the faecal microbiota obtained by Denaturing Gradient Gel Electrophoresis (DGGE) of PCR amplified bacterial 16S rRNA genes as well as of Reverse Transcriptase-PCR amplified bacterial 16S rRNA resulted in different phylogenetic profiles for each of the five animal groups as revealed by Principal Component Analysis (PCA) of band patterns. CONCLUSION: Even though sucrose and cornstarch are both easily digestible and are not expected to reach the large intestine, the DGGE band patterns obtained indicated that these carbohydrates indeed affected the composition of bacteria in the large gut. Also the two fructans resulted in completely different molecular fingerprints of the faecal microbiota, indicating that even though they are chemically similar, different intestinal bacteria ferment them. Comparison of DNA-based and RNA-based profiles suggested that two species within the phylum Bacteroidetes were not abundant in numbers but had a particularly high ribosome content in the animals fed with inulin.

Animals↗

PubMed2006

Dietary deprivation of fermented foods causes a fall in innate immune response. Lactic acid bacteria can counteract the immunological effect of this deprivation.

Extrinsic factors such as maternal microbiota, bacterial load of the environment, diet and medication modulate the intestinal microbiota. Maturation and function of the immune system is influenced by established gut microbiota. In this work we describe the immunological effects of the dietary deprivation of fermented foods of healthy volunteers. Significant decreases in faecal lactobacillus and total aerobes counts and concentration of short chain fatty acids were observed following deprivation of fermented food of the normal diet. Moreover, a decrease in phagocytic activity in leukocytes was observed after two weeks of restricted diet. Therefore, the dietary deprivation of fermented foods could induce a decrease in innate immune response that might affect the capacity to respond against infections. The ingestion of a probiotic product containing the strains Lactobacillus gasseri CECT5714 and Lactobacillus coryniformis CECT5711 or a standard yogurt containing a conventional starter Lactobacillus delbrueckii sp. bulgaricus counteracted the fall in the immune response, although the probiotic product was more effective than the standard yogurt.

Adult↗

PubMed2006

Tetracycline resistance in Escherichia coli and persistence in the infantile colonic microbiota.

The ecological impact of antibiotic resistance in the absence of selective pressure has been poorly studied. We assessed the carriage of tetracycline resistance genes, persistence in the microbiota, fecal population counts and virulence factor genes in 309 commensal, intestinal Escherichia coli strains obtained from 128 Swedish infants followed during the first year of life with regular quantitative fecal cultures. No infant was given tetracycline, but 25% received other antibiotics. Tetracycline resistance was identified in 12% of strains, all of which carried either tet(A) (49%) or tet(B) (51%) genes. Resistance to other antibiotics occurred in 50% of tet(A)-positive strains, 42% of tet(B)-positive strains and 13% of tetracycline-sensitive strains. However, colonization with tetracycline-resistant strains was unrelated to treatment with antibiotics. Strains that were tet(B)- or tet(A)-positive carried the genes for P fimbriae and aerobactin, respectively, more often than susceptible strains. Tetracycline-resistant and -susceptible strains were equally likely to persist among the intestinal microbiota for > or = 3 weeks and had similar population numbers. However, when a resistant strain and a susceptible strain colonized a child simultaneously, the resistant variety showed lower counts (P = 0.03). In cases of long-term colonization by initially tetracycline-resistant E. coli strains, loss of tet genes occurred in 3 of 13 cases with variable effects on population counts. The results indicate that there is limited pressure against the carriage of tet genes in the infantile gut microbiota even in the absence of antibiotics. Resistant strains may possess colonization factors that balance the cost of producing resistance elements.

Colon↗

PubMed2005

Fructooligosaccharides and fiber partially prevent the alterations in fecal microbiota and short-chain fatty acid concentrations caused by standard enteral formula in healthy humans.

The intestinal microbiota are important during enteral tube feeding because they exert colonization resistance and produce SCFAs. However, the effect of the enteral formula composition on major bacterial groups of the microbiota has not been clearly defined. The aim of this study was to investigate the effect of enteral formulas with and without prebiotic fructooligosaccharides (FOS) and fiber on the fecal microbiota and SCFAs. Healthy subjects (n = 10; 4 men, 6 women) consumed both a standard enteral formula and one containing FOS (5.1 g/L) and fiber (8.9 g/L) as a sole source of nutrition for 14 d in a randomized, double-blind, crossover trial with a 6-wk washout phase. Fecal samples were collected at the start and end of each formula phase, and were analyzed for major bacterial groups and SCFA concentrations using fluorescent in situ hybridization and GLC, respectively. Although there were reductions in total fecal bacteria due to both formula treatments, concentrations were higher after the FOS/fiber formula period compared with the standard formula period (11.2 +/- 0.2 vs. 11.0 +/- 0.2 log(10) cells/g, P = 0.005). The FOS/fiber formula increased bifidobacteria (P = 0.004) and reduced clostridia (P = 0.006). Compared with the standard formula, the FOS/fiber formula resulted in higher concentrations of total SCFA (332.4 +/- 133.8 vs. 220.1 +/- 124.5 micromol/g, P = 0.022), acetate (219.6 +/- 96.3 vs. 136.8 +/- 74.5 micromol/g, P = 0.034) and propionate (58.4 +/- 37.4 vs. 35.6 +/- 25.5 micromol/g, P = 0.02). This study demonstrates that standard enteral formula leads to adverse alterations to the fecal microbiota and SCFA concentrations in healthy subjects, and these alterations are partially prevented by fortification of the formula with FOS and fiber.

Bacteria↗

PubMed2005

Adhesion of bacteria to resected human colonic tissue: quantitative analysis of bacterial adhesion and viability.

Adhesion to the intestinal mucosa is considered to be one of the main selection criteria of lactic acid bacteria for probiotic use. Adhesive probiotics are, for example, considered to provide better antagonism against pathogenic bacteria when compared to non-adhesive strains. Here a new model is described for studying adhesion and interaction of probiotic and pathogenic bacteria in the intestinal mucus in which the intestinal microbiota is present. The model is based on the use of human intestinal tissue, fluorescent-tagged bacteria and confocal laser scanning microscopy (CLSM) in adhesion measurements as well as human intestinal mucus and bioluminescent-tagged bacteria in viability measurements. Use of CLSM enabled, for the first time, real-time three-dimensional observations of live probiotic bacteria in their natural environment, the intestinal mucosa. When the real-time measurement of bacterial adhesion was combined with the real-time sensitive measurement of bacterial viability, it could be studied whether or not the adherent pathogens were alive. The model was used to study the interaction between Lactobacillus rhamnosus GG and Salmonella enterica serovar Typhimurium. We show that L. rhamnosus GG did not affect the adhesion or the viability of S. enterica serovar Typhimurium. Instead S. enterica serovar Typhimurium was shown to decrease the adhesion of L. rhamnosus GG in displacement assays. Moreover, the method is suitable for studies in which the interaction of two or more bacteria is examined in an environment in which other bacteria are present.

Bacterial Adhesion↗

PubMed2007

Toll-like receptor signaling in intestinal epithelial cells contributes to colonic homoeostasis.

PURPOSE OF REVIEW: Since intestinal epithelium expresses Toll-like receptors, it was suggested that the intestinal epithelium is actively involved in the maintenance of colonic homeostasis. Here we describe our recent findings, which support an active contribution of colonic epithelium to intestinal homeostasis via a unique activation of epithelial TLR9. RECENT FINDINGS: Recent data indicate that stimulation of Toll-like receptors by intestinal microbiota supports colonic homeostasis. Several Toll-like receptors are expressed in intestinal epithelium. TLR9, an intracellular protein in immune cells, is expressed on the cell surfaces of intestinal epithelium, both on the apical and the basolateral membrane. TLR9 signaling varies in a domain-specific manner; whereas JNK is activated by TLR9 ligand both apically or basolaterally, NF-kappaB is activated only via basolateral stimulation. In apical TLR9 stimulation, IkappaB is phosphorylated and ubiquitinated but is not degraded, and NF-kappaB-dependent inflammatory signals are not transduced. Stimulation of apical TLR9 compromises the inflammatory cascade induced basolaterally by several other Toll-like receptor ligands, suggesting that apical exposure to luminal microbial DNA restrains intestinal inflammation. SUMMARY: These data indicate that certain luminal bacterial products support colonic homeostasis via activation of epithelial Toll-like receptors. The role of epithelial Toll-like receptor expression and activation in the pathogenesis of human inflammatory bowel disease is yet to be explored.

Animals↗

PubMed2026

Metagenomic profiling of gut microbiome in post-cholecystectomy patients with diarrhea: a nested case-control study.

BACKGROUND: Cholecystectomy can cause diarrhea, with an incidence as high as 57.2%, seriously impacting patient prognosis. To investigate the gut dysbiosis following cholecystectomy and identify microbial biomarkers and functional genomics associated with post-cholecystectomy diarrhea (PCD), we conducted a nested case-control study within a prospective cohort. METHODS: We enrolled a cohort of 160 patients. At follow-up completion, 30 patients who developed PCD were matched with 30 non-PCD (NPCD) controls. 16 S rRNA sequencing was used to analyze gut microbiota structure and diversity (mainly at genus level). Representative fecal samples underwent metagenomic sequencing for species level and genetic differential analysis. RESULTS: The potentially pathogenic bacterial species Coprococcus comes and Blautia sp. were significantly enriched in the gut microbiota of PCD patients, with their abundance positively correlated with the degree of intestinal inflammation. In contrast, the potentially beneficial bacterial species Bacteroides intestinalis and Prevotella copri, known to contribute to lipid metabolism and play a role in modulating gut immunity and suppressing inflammatory responses, were found to be significantly depleted in PCD patients. Further metagenomic functional analysis revealed significant enrichment of pathways related to cell motility, membrane transport, and sulfur metabolism in PCD patients. CONCLUSIONS: This work identified potential beneficial and pathogenic bacterial species associated with the onset of PCD, as well as significantly enriched functional pathways within the intestinal microbiota. These findings provide a scientific basis for elucidating the relationship between PCD and gut microbiota, and provide candidate microbial signatures and functional pathways that may inform future microbiota-targeted strategies, pending external and mechanistic validation.

Humans↗

PubMed2006

Gut microbiota composition and development of atopic manifestations in infancy: the KOALA Birth Cohort Study.

BACKGROUND AND AIMS: Perturbations in intestinal microbiota composition due to lifestyle changes may be involved in the development of atopic diseases. We examined gut microbiota composition in early infancy and the subsequent development of atopic manifestations and sensitisation. METHODS: The faeces of 957 infants aged 1 month and participating in the KOALA Birth Cohort Study were analysed using quantitative real-time PCR. Information on atopic symptoms (eczema, wheeze) and potential confounders was acquired through repeated questionnaires. Total and specific IgE were measured in venous blood samples collected during home visits when the infant was 2 years old. During these home visits a clinical diagnosis of atopic dermatitis was made according to the UK-Working Party criteria. RESULTS: The presence of Escherichia coli was associated with a higher risk of developing eczema (OR(adj) = 1.87; 95% CI 1.15 to 3.04), this risk being increased with increasing numbers of E coli (p(for trend) = 0.016). Infants colonised with Clostridium difficile were at higher risk of developing eczema (OR(adj) = 1.40; 95% CI 1.02 to 1.91), recurrent wheeze (OR(adj) = 1.75; 95% CI 1.09 to 2.80) and allergic sensitisation (OR(adj) = 1.54; 95% CI 1.02 to 2.31). Furthermore, the presence of C difficile was also associated with a higher risk of a diagnosis of atopic dermatitis during the home visit (OR(adj) = 1.73; 95% CI 1.08 to 2.78). CONCLUSION: This study demonstrates that differences in gut microbiota composition precede the development of atopy. Since E coli was only associated with eczema and C difficile was associated with all atopic outcomes, the underlying mechanisms explaining these association may be different.

Bacteria↗

PubMed2006

Culture-independent analysis of indomethacin-induced alterations in the rat gastrointestinal microbiota.

Nonsteroidal anti-inflammatory drugs (NSAIDs) are commonly prescribed for a variety of inflammatory conditions; however, the benefits of this class of drugs are accompanied by deleterious side effects, most commonly gastric irritation and ulceration. NSAID-induced ulceration is thought to be exacerbated by intestinal microbiota, but previous studies have not identified specific microbes that contribute to these adverse effects. In this study, we conducted a culture-independent analysis of approximately 1,400 bacterial small-subunit rRNA genes associated with the small intestines and mesenteric lymph nodes of rats treated with the NSAID indomethacin. This is the first molecular analysis of the microbiota of the rat small intestine. A comparison of clone libraries and species-specific quantitative PCR results from rats treated with indomethacin and untreated rats revealed that organisms closely related to Enterococcus faecalis were heavily enriched in the small intestine and mesenteric lymph nodes of the treated rats. These data suggest that treatment of NSAID-induced ulceration may be facilitated by addressing the microbiological imbalances.

Animals↗