BackgroundGut microbes influence animal health and thus, are potential targets for interventions that slow aging. Live E. coli provides the nematode worm Caenorhabditis elegans with vital micronutrients, such as folates that cannot be synthesized by animals. However, the microbe also limits C. elegans lifespan. Understanding these interactions may shed light on how intestinal microbes influence mammalian aging.ResultsSerendipitously, we isolated an E. coli mutant that slows C. elegans aging. We identified the disrupted gene to be aroD, which is required to synthesize aromatic compounds in the microbe. Adding back aromatic compounds to the media revealed that the increased C. elegans lifespan was caused by decreased availability of para-aminobenzoic acid, a precursor to folate. Consistent with this result, inhibition of folate synthesis by sulfamethoxazole, a sulfonamide, led to a dose-dependent increase in C. elegans lifespan. As expected, these treatments caused a decrease in bacterial and worm folate levels, as measured by mass spectrometry of intact folates. The folate cycle is essential for cellular biosynthesis. However, bacterial proliferation and C. elegans growth and reproduction were unaffected under the conditions that increased lifespan.ConclusionsIn this animal:microbe system, folates are in excess of that required for biosynthesis. This study suggests that microbial folate synthesis is a pharmacologically accessible target to slow animal aging without detrimental effects.

SummaryFolates are cofactors for biosynthetic enzymes in all eukaryotic and prokaryotic cells. Animals cannot synthesize folate and must acquire it from their diet or microbiota. Previously, we showed that inhibiting E. coli folate synthesis increases C. elegans lifespan. Here, we show that restriction or supplementation of C. elegans folate does not influence lifespan. Thus, folate is required in E. coli to shorten worm lifespan. Bacterial proliferation in the intestine has been proposed as a mechanism for the life-shortening influence of E. coli. However, we found no correlation between C. elegans survival and bacterial growth in a screen of 1,000+ E. coli deletion mutants. Nine mutants increased worm lifespan robustly, suggesting specific gene regulation is required for the life-shortening activity of E. coli. Disrupting the biosynthetic folate cycle did not increase lifespan. Thus, folate acts through a growth-independent route in E. coli to accelerate animal aging.

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Diarrhoea is a common problem in dogs and can result in disturbance of the normal intestinal microbiota. However, little is known about the gastrointestinal microbiota of dogs with chronic diarrhoea and controlled canine studies of dietary management are scarce. The aims of this study were to investigate the predominant faecal microbiota of chronic diarrhoea dogs and to examine the effect(s) of a fibre blend on the canine faecal microbiota. A 3-week fibre supplementation feeding study was performed in nine chronic diarrhoea and eight control dogs. Atopobium cluster, Lactobacillus-Enterococcus group and Clostridium cluster XIV were the predominant bacterial groups in all dogs. Chronic diarrhoea dogs had significantly higher Bacteroides counts at baseline and significantly lower Atopobium cluster counts following fibre supplementation compared with control dogs. Atopobium cluster levels increased significantly in control dogs, while counts of sulphatereducing bacteria decreased significantly and Clostridium clusters I and II counts increased significantly in chronic diarrhoea dogs during fibre supplementation. Microbial profiles (detected by denaturing gradient gel electrophoresis) demonstrated interindividual variation, with greater similarity seen between the chronic diarrhoea and control dogs' profiles after fibre supplementation compared with baseline. In conclusion, fibre supplementation induced changes in the canine faecal microbiota, with greater resemblance between the microbiota of chronic diarrhoea and control dogs after this dietary modulation.

Weaning is a stressful process for kittens and is often associated with diarrhoea and the onset of infectious diseases. The gastrointestinal (GI) microbiota plays an essential role in host well-being, including improving homoeostasis. Composition of the GI microbiota of young cats is poorly understood and the impact of diet on the kitten microbiota unknown. The aims of this study were to monitor the faecal microbiota of kittens and determine the effect(s) of diet on its composition. Bacterial succession was monitored in two groups of kittens (at 4 and 6 weeks, and 4 and 9 months of age) fed different foods. Age-related microbial changes revealed significantly different counts of total bacteria, lactic acid bacteria, Desulfovibrionales, Clostridium cluster IX and Bacteroidetes between 4-week- and 9-month-old kittens. Diet-associated differences in the faecal microbiota of the two feeding groups were evident. In general, fluorescence in situ hybridization analysis demonstrated bifidobacteria, Atopobium group, Clostridium cluster XIV and lactic acid bacteria were dominant in kittens. Denaturing gradient gel electrophoresis profiling showed highly complex and diverse faecal microbiotas for kittens, with age- and/or food-related changes seen in relation to species richness and similarity indices. Four-week-old kittens harboured more diverse and variable profiles than those of weaned kittens.

Aims:  Aim of the study was to investigate the faecal microbiota of geriatric cats, as aging affects the nutrient digestibility and metabolic function of the feline intestine. Methods and Results:  Twenty geriatric cats were randomly assigned to two groups that were fed different foods. Coriobacteriaceae, Clostridium cluster XIV, bifidobacteria and lactic acid bacteria were the dominant faecal bacterial groups, accounting for c. 40% of total bacteria. Clostridium cluster IX was less predominant (0·5% of total bacteria), while the remaining bacterial populations enumerated only accounted for 0·2% of total bacteria. Highly diverse microbial profiles were demonstrated for geriatric cats with denaturing gradient gel electrophoresis, although a few common bands were evident. Some differences were seen in the feline faecal microbiota between animal groups at the same time or over time for individual animals. However, no obvious clustering based on animal group or sample time was indicated. Conclusions:  Geriatric cats harboured a complex faecal microbiota and c. 41% of total bacteria have been detected with the probes employed. Significance and Impact of the Study:  First molecular‐based study examining faecal microbiota of geriatric felines. Knowledge of the microbiota associated with ageing in cats may allow improved development of foods specific for the needs of senior cats.

Background: The early-life gut microbiota, which is critically important for the long-term health of infants, is normally sensitive to perturbations, especially in preterm infants. However, how the gut microbiota develops and what key factors affect the preterm gut microbiota remain largely unknown. We hypothesized that preterm microbial dysbiosis exists from the beginning after birth, and microbial alteration is associated with parenteral nutrition and antibiotic therapy interventions. Methods: Fecal samples were collected from fifty-one preterm and fifty full-term vaginally delivered (FTVD) infants at 7 time points for 90 days after birth. The microbial profiles of 558 fecal DNA samples were analyzed by sequencing their 16S ribosomal RNA amplicons. A random-effects generalized least square regression was used to identify factors that influence the bacterial composition over time. Results: The altered gut microbiota in preterm infants existed from the meconium, having significantly lower levels of Escherichia-Shigella than those in FTVD infants. The developmental trajectories of 7 predominant bacterial groups successfully fitted with exponential/linear function curves (R 2 , 0.921-0.993) in both groups. By day 90, depleted levels of Bacteroides and Parabacteroides and an overabundance of Peptoclostridium were characteristic of the preterm group. The prolonged use of antibiotics and parenteral nutrition had significant adverse effects on the Lactobacillus and Bifidobacterium levels in preterm infants. Moreover, gestational age, sex, and birth weight were factors impacting specific genera in preterm infants. Conclusion: The early-life microbial composition and functions were markedly different in preterm infants, being associated with the prolonged use of postnatal antibiotics and parenteral nutrition.

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