The Germfree Animal in Nutritional Studies

Wostmann, Bernard S.

doi:10.1146/annurev.nu.01.070181.001353

Cited by 164 publications

(137 citation statements)

References 57 publications

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“…Differential activation of TGR5 by variations in the bile acid pool between GF and CV rats may manifest in differences in energy expenditure. Indeed, GF animals are characterized by a lower basal metabolic rate compared with their CV equivalents (40). Recent work has confirmed an association between microbial composition and obesity (2, 4) mediated through several mechanisms such as increased fat storage through fastinginduced adipocyte factor (fiaf) suppression (41), increased energy harvest from the diet, and reduced fatty acid oxidation (42).…”

Section: Discussionmentioning

confidence: 99%

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Systemic gut microbial modulation of bile acid metabolism in host tissue compartments

Swann

Want

Geier

et al. 2010

Proc. Natl. Acad. Sci. U.S.A.

644

476

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We elucidate the detailed effects of gut microbial depletion on the bile acid sub-metabolome of multiple body compartments (liver, kidney, heart, and blood plasma) in rats. We use a targeted ultraperformance liquid chromatography with time of flight mass-spectrometry assay to characterize the differential primary and secondary bile acid profiles in each tissue and show a major increase in the proportion of taurine-conjugated bile acids in germ-free (GF) and antibiotic (streptomycin/penicillin)-treated rats. Although conjugated bile acids dominate the hepatic profile (97.0 ± 1.5%) of conventional animals, unconjugated bile acids comprise the largest proportion of the total measured bile acid profile in kidney (60.0 ± 10.4%) and heart (53.0 ± 18.5%) tissues. In contrast, in the GF animal, taurine-conjugated bile acids (especially taurocholic acid and tauro-β-muricholic acid) dominated the bile acid profiles (liver: 96.0 ± 14.5%; kidney: 96 ± 1%; heart: 93 ± 1%; plasma: 93.0 ± 2.3%), with unconjugated and glycine-conjugated species representing a small proportion of the profile. Higher free taurine levels were found in GF livers compared with the conventional liver (5.1-fold; P < 0.001). Bile acid diversity was also lower in GF and antibiotic-treated tissues compared with conventional animals. Because bile acids perform important signaling functions, it is clear that these chemical communication networks are strongly influenced by microbial activities or modulation, as evidenced by farnesoid X receptor-regulated pathway transcripts. The presence of specific microbial bile acid co-metabolite patterns in peripheral tissues (including heart and kidney) implies a broader signaling role for these compounds and emphasizes the extent of symbiotic microbial influences in mammalian homeostasis.farnesoid X receptor | gut microbiota | TGR5 | ultra-performance liquid chromatography mass spectrometry | G protein-coupled bile acid receptor 1 T he importance of gut microbiome variation in relation to human health and diverse diseases is now well-recognized (1-4). The microbiome is a virtual organ that performs many digestive and metabolic functions for the host, including enhanced calorific recovery from ingested foods and degradation of complex plant polysaccharides. Microbial communities have coevolved with man and show remarkable diversity dependent on topographical location and interperson variability (5). Co-evolution has refined the microbiome of organisms to a state where metabolic complementarity exists within the microbiota (6), and important biosynthetic/ metabolic pathways are provided for the host that significantly extend host metabolic capacity (3). As such, the mammalian host can be considered a superorganism (7), whose metabolism is the sum of that of both the host and the collective microbial community. The enterohepatic circulation provides a vehicle for this transgenomic metabolism, and bile acids, whose functional role in the global mammalian system is multifaceted, are an important class of metabolites that u...

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Section: Discussionmentioning

confidence: 99%

“…GF animals have smaller hearts, livers, and lungs compared with CV animals, with a significantly reduced metabolic rate, lower oxygen consumption, and reduced cardiac output (40). Recent work by Crawford et al (56) implicated myocardial ketone body metabolism in this reduced myocardial-mass phenotype observed in GF mice.…”

Section: Discussionmentioning

confidence: 99%

Systemic gut microbial modulation of bile acid metabolism in host tissue compartments

Swann

Want

Geier

et al. 2010

Proc. Natl. Acad. Sci. U.S.A.

644

476

View full text Add to dashboard Cite

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“…In fact, vitamin synthesis by the intestinal microflora has been recognized since at least 1934, when Fildes wrote, "It is not impossible that substances shown by the bacterial chemist to be necessary for the proper growth of bacteria may subsequently be found to be necessary for the growth of animals" (33). A key example of the importance of this metabolic relationship was the finding that germfree mice require supplementation with vitamin K and some B vitamins (i.e., folate, B 12 , and biotin) since these vitamins are microbially derived products (6,155). Indeed, these vitamins are synthesized by several intestinal genera, including Bacteroides, Eubacterium, Propionibacterium, and Fusobacterium.…”

Section: Role Of the Colonizing Bacteria In The Gastrointestinal Tractmentioning

confidence: 99%

Bacteria in the Intestine, Helpful Residents or Enemies from Within?

2008

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“…The significance of the protective role of the GM has been highlighted by the profound impact seen when the GM is absent or disrupted. Germ-free mice have poorly developed mucosal architecture and rudimentary development of the mucosa-associated lymphoid tissue, being generally small and underweight, and also highly susceptible to intestinal infection (10) .In obese patients, there is a significant change in the composition of the GM compared with lean controls (11,12) , and, in rats, these modifications can be induced by the ingestion of a HFD (13) . Furthermore, host nutritional status may be markedly influenced by the composition and activities of the GM since the Bacteroidetes:Firmicutes ratio seems to be decreased in obese individuals and genetically obese mice harbour an 'obese microbiome', with a transferable elevated capacity for energy sequestration (14) .…”

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confidence: 99%

Changes in gut microbiota due to supplemented fatty acids in diet-induced obese mice

et al. 2013

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Consumption of a high-fat diet (HFD), which is associated with chronic 'low-grade' systemic inflammation, alters the gut microbiota (GM). The aim of the present study was to investigate the ability of an oleic acid-derived compound (S1) and a combination of n-3 fatty acids (EPA and DHA, S2) to modulate both body weight and the GM in HFD-induced obese mice. A total of eighty mice were fed either a control diet or a HFD, non-supplemented or supplemented with S1 or S2. At week 19, faeces were collected in order to analyse the GM. Groupspecific primers for accurate quantification of several major bacterial groups from faecal samples were assayed using quantitative PCR. The HFD induced an increase in body weight, which was reduced by supplementation with S1. Furthermore, S1 supplementation markedly increased total bacterial density and restored the proportions of bacteria that were increased (i.e. clostridial cluster XIVa and Enterobacteriales) or decreased (i.e. Bifidobacterium spp.) during HFD feeding. S2 supplementation significantly increased the quantities of Firmicutes (especially the Lactobacillus group). Correlation analysis revealed that body weight correlated positively with the phylum Firmicutes and clostridial cluster XIVa, and negatively with the phylum Bacteroidetes. In conclusion, the consumption of a HFD induced changes in the faecal microbiota, which were associated with the appearance of an obese phenotype. Supplementation of the HFD with S1 counteracted HFD-induced gut dysbiosis, together with an improvement in body weight. These data support a role for certain fatty acids as interesting nutrients related to obesity prevention.Key words: Gut microbiota: Fatty acids: Obese mice: Quantitative PCR The worldwide prevalence of overweight and obesity has increased dramatically in the past decades, reaching epidemic levels (1) . It is well known that a high-fat diet (HFD) leads, especially in genetically predisposed individuals, to an accumulation of adipose tissue (2) and to the development of a cluster of metabolic and cardiovascular disorders such as type 2 diabetes, atherosclerosis, hypertension and stroke (3) .The gut microbiota (GM) has an important role in supplying nutrients and vitamins, giving colonisation resistance against pathogenic bacteria and interacting with the host immune system and intestinal epithelium (4) . The possible involvement of the host genotype, particularly as it relates to immunophenotype, has been frequently postulated as a major influence on GM composition and stability. Other variables known to broadly influence the composition of the GM include the type of delivery (vaginal or caesarean), age, the use of antibiotics and other drugs, and 'lifestyle' (such as diet, physical activity and stress) (5 -9) . The significance of the protective role of the GM has been highlighted by the profound impact seen when the GM is absent or disrupted. Germ-free mice have poorly developed mucosal architecture and rudimentary development of the mucosa-associated lymphoid tissue, b...

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The Germfree Animal in Nutritional Studies

Cited by 164 publications

References 57 publications

Systemic gut microbial modulation of bile acid metabolism in host tissue compartments

Systemic gut microbial modulation of bile acid metabolism in host tissue compartments

Bacteria in the Intestine, Helpful Residents or Enemies from Within?

Changes in gut microbiota due to supplemented fatty acids in diet-induced obese mice

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