The use of rats associated with a human faecal flora as a model for studying the effects of diet on the human gut microflora

Mallett, A.K.; Bearne, C.A.; Rowland, Ian; Farthing, M. J. G.; Cole, Christopher B.; Fuller, R.

doi:10.1111/j.1365-2672.1987.tb02415.x

Cited by 93 publications

(57 citation statements)

References 19 publications

(12 reference statements)

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“…As cefquinome is mainly used in pigs, and because the intestinal flora is very different between rats and pigs, we used a model of gnotobiotic rats harboring porcine fecal flora samples enriched with a CTX-R E. coli strain. Indeed, it has been shown that the implanted flora were stable and comparable to natural flora from the sampled individuals (24,25). No measurable enrichment of CTX-R Enterobacteriaceae was observed with the prepatent phase adjusted dose, whereas rapid and massive amplification of CTX-R Enterobacteriaceae was observed with the patent phase adjusted dose.…”

Section: Discussionmentioning

confidence: 96%

Low or High Doses of Cefquinome Targeting Low or High Bacterial Inocula Cure Klebsiella pneumoniae Lung Infections but Differentially Impact the Levels of Antibiotic Resistance in Fecal Flora

Vasseur

Laurentie

Rolland

et al. 2014

Antimicrob Agents Chemother

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The combination of efficacious treatment against bacterial infections and mitigation of antibiotic resistance amplification in gut microbiota is a major challenge for antimicrobial therapy in food-producing animals. In rats, we evaluated the impact of cefquinome, a fourth-generation cephalosporin, on both Klebsiella pneumoniae lung infection and intestinal flora harboring CTX-Mproducing Enterobacteriaceae. Germfree rats received a fecal flora specimen from specific-pathogen-free pigs, to which a CTX-M-producing Escherichia coli strain had been added. K. pneumoniae cells were inoculated in the lungs of these gnotobiotic rats by using either a low (10 5 CFU) or a high (10 9 CFU) inoculum. Without treatment, all animals infected with the low or high K. pneumoniae inoculum developed pneumonia and died before 120 h postchallenge. In the treated groups, the low-inoculum rats received a 4-day treatment of 5 mg/kg of body weight cefquinome beginning at 24 h postchallenge (prepatent phase of the disease), and the high-inoculum rats received a 4-day treatment of 50 mg/kg cefquinome beginning when the animals expressed clinical signs of infection (patent phase of the disease). The dose of 50 mg/kg targeting the high K. pneumoniae inoculum cured all the treated rats and resulted in a massive amplification of CTX-M-producing Enterobacteriaceae. A dose of 5 mg/kg targeting the low K. pneumoniae inoculum cured all the rats and averted an outbreak of clinical disease, all without any amplification of CTX-M-producing Enterobacteriaceae. These findings might have implications for the development of new antimicrobial treatment strategies that ensure a cure for bacterial infections while avoiding the amplification of resistance genes of human concern in the gut microbiota of food-producing animals.A ntimicrobial resistance is a major threat to human health, and the overuse of antibiotics in both human patients and animals is considered to be the main factor leading to the selection of resistant bacteria. It is also increasingly recognized that the gut microbiota constitutes one of the main reservoirs of resistance genes among commensal bacterial ecosystems (1-4), and that the antibiotic doses currently used in human and animal patients have not been optimized to prevent the collateral selection of antimicrobial resistance in the gut microbiota or its colonization by exogenous resistant strains (3, 5).An examination of the interactions between antibiotics, pathogens, and the commensal flora, as well as an increased understanding of the key factors governing antimicrobial activity and resistance selection, might lead to the development of strategies combining maximal efficacy with minimal impact on the commensal bacterial ecosystems (2, 6, 7). For example, recent studies demonstrated that the degree of amplification of antimicrobial resistance in the gut microbiota was directly correlated with the magnitude of the antibiotic dose, regardless of the route of administration (8, 9).Interestingly, some other studies have shown that the i...

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Section: Discussionmentioning

confidence: 96%

Low or High Doses of Cefquinome Targeting Low or High Bacterial Inocula Cure Klebsiella pneumoniae Lung Infections but Differentially Impact the Levels of Antibiotic Resistance in Fecal Flora

Vasseur

Laurentie

Rolland

et al. 2014

Antimicrob Agents Chemother

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“…Molecular techniques that do not require isolation of bacterial strains, such as ERIC-PCR fingerprinting, TGGE/denaturing gradient gel electrophoresis (DGGE) analysis, 16S rRNA gene clone library profiling and real-time PCR, were utilized to analyze the microbiota in the gut of the HFA piglets. Previous studies on the microbiota composition of HFA animals were based on traditional culture methods (Raibaud et al, 1980;Hazenberg et al, 1981;Mallett et al, 1987;Hirayama, 1999), which underestimate the abundance of the bacterial populations and thus provide an incomplete picture of the composition of the microflora. Use of the abovementioned molecular methods will yield more detailed information about the microbiota and will provide a more comprehensive comparison of the microbiota in the HFA animals and the human donor.…”

Section: Resultsmentioning

confidence: 99%

Inter-species transplantation of gut microbiota from human to pigs

et al. 2007

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Direct research on gut microbiota for understanding its role as 'an important organ' in human individuals is difficult owing to its vast diversity and host specificity as well as ethical concerns. Transplantation of human gut microbiota into surrogate hosts can significantly facilitate the research of human gut ecology, metabolism and immunity but rodents-based model provides results with low relevance to humans. A new human flora-associated (HFA) piglet model was hereby established taking advantage of the high similarity between pigs and humans with respect to the anatomy, physiology and metabolism of the digestive system. Piglets were delivered via cesarean section into a SPF-level barrier system and were inoculated orally with a whole fecal suspension from one healthy 10-year-old boy. The establishment and composition of the intestinal microbiota of the HFA piglets were analyzed and compared with that of the human donor using enterobacterial repetitive intergenic consensus sequence-PCR fingerprinting-based community DNA hybridization, group-specific PCR-temperature gradient gel electrophoresis and real-time PCR. Molecular profiling demonstrated that transplantation of gut microbiota from a human to germfree piglets produced a donor-like microbial community with minimal individual variation. And the microbial succession with aging of those ex-germfree piglets was also similar to that observed in humans. This HFA model provides a significantly improved system for research on gut ecology in human metabolism, nutrition and drug discovery.

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“…HUM mice (ex-GF mice colonized with a human microbiota) are emerging as a powerful model for studying humanrelevant microbes in a controlled experimental setting (Mallett et al, 1987;Bowey et al, 2003). Here we use HUM mice as a model for studying metabolomic changes within urine and feces.…”

Section: Introductionmentioning

confidence: 99%

A metabolomic view of how the human gut microbiota impacts the host metabolome using humanized and gnotobiotic mice

et al. 2013

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Defining the functional status of host-associated microbial ecosystems has proven challenging owing to the vast number of predicted genes within the microbiome and relatively poor understanding of community dynamics and community-host interaction. Metabolomic approaches, in which a large number of small molecule metabolites can be defined in a biological sample, offer a promising avenue to 'fingerprint' microbiota functional status. Here, we examined the effects of the human gut microbiota on the fecal and urinary metabolome of a humanized (HUM) mouse using an optimized ultra performance liquid chromatography-mass spectrometry-based method. Differences between HUM and conventional mouse urine and fecal metabolomic profiles support host-specific aspects of the microbiota's metabolomic contribution, consistent with distinct microbial compositions. Comparison of microbiota composition and metabolome of mice humanized with different human donors revealed that the vast majority of metabolomic features observed in donor samples are produced in the corresponding HUM mice, and individual-specific features suggest 'personalized' aspects of functionality can be reconstituted in mice. Feeding the mice a defined, custom diet resulted in modification of the metabolite signatures, illustrating that host diet provides an avenue for altering gut microbiota functionality, which in turn can be monitored via metabolomics. Using a defined model microbiota consisting of one or two species, we show that simplified communities can drive major changes in the host metabolomic profile. Our results demonstrate that metabolomics constitutes a powerful avenue for functional characterization of the intestinal microbiota and its interaction with the host.

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The use of rats associated with a human faecal flora as a model for studying the effects of diet on the human gut microflora

Cited by 93 publications

References 19 publications

Low or High Doses of Cefquinome Targeting Low or High Bacterial Inocula Cure Klebsiella pneumoniae Lung Infections but Differentially Impact the Levels of Antibiotic Resistance in Fecal Flora

Low or High Doses of Cefquinome Targeting Low or High Bacterial Inocula Cure Klebsiella pneumoniae Lung Infections but Differentially Impact the Levels of Antibiotic Resistance in Fecal Flora

Inter-species transplantation of gut microbiota from human to pigs

A metabolomic view of how the human gut microbiota impacts the host metabolome using humanized and gnotobiotic mice

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