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Investigations on the intestinal microbiome in rabbits - A review
Abstract
One week after weaning the rabbit's intestines are almost functionally mature, although the bacterial diversity can still change. Microorganisms populate the whole gastrointestinal tract, but the highest concentrations can be found in the caecum and colon of rabbits. Besides smaller amounts of archaea, yeasts and protozoa, bacteria account for the majority of microorganisms in the intestines of rabbits. In the first two weeks of the rabbit's life the ratio between facultative and obligatory anaerobes is constant. Then Bacteroides dominate the intestinal microbiome followed by Clostridium, Endosporus and Acuformis. Hard and soft faeces generally differ in bacterial composition, particularly in rabbits with less weight. The occurrence of specific bacteria in hard faeces shows a correlation with the weight of rabbits. Obviously feeding has an effect on intestinal microbes. Restricted feeding for a short-time improved intestinal health. Especially dietary fibre seemed to be suitable to prevent gastrointestinal disturbances in young rabbits. Fibre provides the main energy source for bacteria in the intestine of rabbits. The bacteria, which are able to ferment cellulose, xylane and pectin, established themselves with solid feed intake. An early maturation and thus stabilisation of the microbiome seems to be worthwhile in this early stage of life. High neutral detergent soluble fibre with simultaneously low neutral detergent fibre contents in the diet increase the quantity of bacteria. However, other than the known fibre degrading bacteria like Ruminococcus flavefaciens and Fibrobacter succinogenes, are involved in this fibre decomposition.
... We hypothesized a larger biodiversity (and activity) of the caecal microbiota that would explain the better resistance of the restricted rabbit to digestive trouble around weaning (Combes et al., 2013;Kieckhaven and Wolf, 2016). Since a quantitative restriction with one delivery a day improves the digestibility and increases the retention time in the hind gut, we expected a stimulated microbial activity in the caecum. ...
Postweaning feed restriction preserves rabbit digestive health after weaning, but the underlying physiological mechanisms are not yet understood. To elucidate whether the feeding intake pattern modification related to feed restriction might be involved, we studied the effects of both feed intake quantity and intake frequency. Animals were allotted at weaning (28 d old) in a 2 × 2 factorial design: feed intake quantity (AL = ad libitum vs R = 75% of AL) and fragmented feed distribution (FFD) (1 vs 13 distributions), thus forming four groups (AL1, AL13, R1 and R13). New Zealand White growing rabbits were used from weaning to slaughter (70 d old), to analyse mortality, morbidity, performance, intake behaviour, digestion and microbial activity. Seven days after starting feed restriction (35 d old, group R1), rabbits consumed 44% of the feed within 2 h, 65% in 4 h and in 7 h over 95%. Over the 28–70 d period, mortality was low (5.3%) while morbidity averaged 18.5% and neither was affected by treatment. However, FFD tended to decrease the morbidity rate during the first 14 days after weaning (P = 0.06). Feed conversion (28–70 d) was improved by restriction (+15%, P
... Although the panda cubs were trained to eat bamboo after 1 year of age, they mainly played with biting it first. The increase in bacterial and fungal richness in the two pandas were associated with food supplementation (Kieckhven and Wolf, 2016;Stephens et al., 2016;Williams et al., 2018;Guevarra et al., 2019). We continuously monitored the marked fluctuation of bacterial diversity and relative abundances after the pandas were 1.5 years old and the bacterial community stabilized when pandas had adapted to a specialized bamboo diet after they were 2 years old, differing from those of Zhang et al. (2018). ...
Adaptation to a bamboo diet is an essential process for giant panda growth, and gut microbes play an important role in the digestion of the polysaccharides in bamboo. The dietary transition in giant panda cubs is particularly complex, but it is an ideal period in which to study the effects of gut microbes on polysaccharide use because their main food changes from milk to bamboo (together with some bamboo shoot and coarse pastry). Here, we used 16S rDNA and internal transcribed spacer 1 (ITS1) DNA sequencing and metagenomic sequencing analysis to investigate the succession of the gut microbial structure in feces sampled from twin giant panda cubs during the completely dietary transition and determine the abundances of polysaccharide-metabolizing genes and their corresponding microbes to better understand the degradation of bamboo polysaccharides. Successive changes in the gut microbial diversity and structure were apparent in the growth of pandas during dietary shift process. Microbial diversity increased after the introduction of supplementary foods and then varied in a complex way for 1.5–2 years as bamboo and complex food components were introduced. They then stabilized after 2 years, when the cubs consumed a specialized bamboo diet. The microbes had more potential to metabolize the cellulose in bamboo than the hemicellulose, providing genes encoding cellulase systems corresponding to glycoside hydrolases (GHs; such as GH1, GH3, GH5, GH8, GH9, GH74, and GH94). The cellulose-metabolizing species (or genes) of gut bacteria was more abundant than that of gut fungi. Although cellulose-metabolizing species did not predominate in the gut bacterial community, microbial interactions allowed the giant pandas to achieve the necessary dietary shift and ultimately adapt to a bamboo diet.
Rex rabbit is an important small herbivore for fur and meat production. However, little is known about the gut microbiota in rex rabbit, especially regarding their relationship with different fecal types and growth of the hosts. We characterized the microbiota of both hard and soft feces from rex rabbits with high and low body weight by using the Illumina MiSeq platform targeting the V4 region of the 16S rDNA. High weight rex rabbits possess distinctive microbiota in hard feces, but not in soft feces, from the low weight group. We detected the overrepresentation of several genera such as YS2/Cyanobacteria, and Bacteroidales and underrepresentation of genera such as Anaeroplasma spp. and Clostridiaceae in high weight hard feces. Between fecal types, several bacterial taxa such as Ruminococcaceae, and Akkermansia spp. were enriched in soft feces. PICRUSt analysis revealed that metabolic pathways such as "stilbenoid, diarylheptanoid, gingerol biosynthesis" were enriched in high weight rabbits, and pathways related to "xenobiotics biodegradation" and "various types of N-glycan biosynthesis" were overrepresented in rabbit soft feces. Our study provides foundation to generate hypothesis aiming to test the roles that different bacterial taxa play in the growth and caecotrophy of rex rabbits.
Enteric diseases frequently occur in rabbits around weaning leading to extensive use of antibiotics in rabbit breeding. In this context, breeders as well as consumers ask for alternative strategies that improve the health of animals. But the maintenance of gut health is complex and relies on a delicate balance between the mucosa (including the absorptive epithelium and the digestive immune system), the gut microbiota and environmental factors including diet. Firstly, immune and non-immune mechanisms of protection against pathogens in the gut are presented, in relation with the installation and composition of the gut microbial ecosystem in the rabbit and its role on health. Finally, several strategies to stimulate digestive immune system or favour beneficial microbiota to exclude enteric pathogens were discussed. Several nutrients including fatty acids and fibres, were implicated in the development of immune response and could be used to improve immune ability of animals. Dietary fatty acids (ω3/ω6 ratio) could be of interest in the rabbit. The role of dietary fibre on digestive health has been demonstrated in weaned rabbits, and strong relations between fibre supply and cæcal microbiota were evidenced. Some works also reported an influence of fibre level in the diet given to the young before weaning on health status of rabbits after weaning. Therefore, nutritional needs of suckling rabbits, more especially fibre requirements, to enhance subsequent gut health need to be thoroughly studied, in relation with needs of their mothers. Exogenous flora could also be added to the diet to stimulate the digestive immune system and prevent the development of enteric pathogens. Finally, vaccines permit protection of the host against specific pathogens.
In rabbits, the bacterial and archaeal community of caecal ecosystem is composed mostly of species not yet described and very specific to that species. In mammals, the digestive ecosystem plays important physiological roles: hydrolysis and fermentation of nutrients, immune system regulation, angiogenesis, gut development and acting as a barrier against pathogens. Understanding the functioning of the digestive ecosystem and how to control its functional and specific diversity is a priority, as this could provide new strategies to improve the resistance of the young rabbit to digestive disorders and improve feed efficiency. This review first recalls some facts about the specificity of rabbit digestive microbiota composition in the main fermentation compartment, and its variability with some new insights based on recent molecular approaches. The main functions of the digestive microbiota will then be explained. Finally, some possible ways to control rabbit caecal microbiota will be proposed and a suitable timing for action will be defined.
This review aims to present the different effects produced by a post-weaning intake limitation strategy on the growing rabbit, now largely used by French professional rabbit breeders. Although a quantitative feed restriction leads to slower growth, feed conversion (FC) is improved, particularly when the rabbits are again fed freely, as compensatory growth occurs. This better FC or the healthy rabbit is because of better digestion resulting from slower passage through the intestine, whereas the digestive physiology is slightly modified (morphometry of the intestinal mucosa, fermentation pattern, microbiota). Meat quality and carcass characteristics are not greatly affected by feed restriction, except for a lower dressing-out percentage. One of the main advantages of limiting post-weaning intake of the rabbit is to reduce the mortality and morbidity rate due to digestive disorders (particularly epizootic rabbit enteropathy syndrome). The consequences for animal welfare are debatable, as feed restriction probably leads to hunger, but it reduces the incidence of digestive troubles after weaning. However, the growing rabbit adapts very well to an intake limitation strategy, without any aggressive behaviour for congener. In conclusion, restriction strategies could improve profitability of rabbit breeding, but they should be adapted to any specific breeding situation, according to the national market, feed prices, etc.
Antibiotics administered in low doses have been widely used as growth promoters in the agricultural industry since the 1950s, yet the mechanisms for this effect are unclear. Because antimicrobial agents of different classes and varying activity are effective across several vertebrate species, we proposed that such subtherapeutic administration alters the population structure of the gut microbiome as well as its metabolic capabilities. We generated a model of adiposity by giving subtherapeutic antibiotic therapy to young mice and evaluated changes in the composition and capabilities of the gut microbiome. Administration of subtherapeutic antibiotic therapy increased adiposity in young mice and increased hormone levels related to metabolism. We observed substantial taxonomic changes in the microbiome, changes in copies of key genes involved in the metabolism of carbohydrates to short-chain fatty acids, increases in colonic short-chain fatty acid levels, and alterations in the regulation of hepatic metabolism of lipids and cholesterol. In this model, we demonstrate the alteration of early-life murine metabolic homeostasis through antibiotic manipulation.
Gut microbial induction of host immune maturation exemplifies host-microbe mutualism. We colonized germ-free (GF) mice with mouse microbiota (MMb) or human microbiota (HMb) to determine whether small intestinal immune maturation depends on a coevolved host-specific microbiota. Gut bacterial numbers and phylum abundance were similar in MMb and HMb mice, but bacterial species differed, especially the Firmicutes. HMb mouse intestines had low levels of CD4(+) and CD8(+) T cells, few proliferating T cells, few dendritic cells, and low antimicrobial peptide expression--all characteristics of GF mice. Rat microbiota also failed to fully expand intestinal T cell numbers in mice. Colonizing GF or HMb mice with mouse-segmented filamentous bacteria (SFB) partially restored T cell numbers, suggesting that SFB and other MMb organisms are required for full immune maturation in mice. Importantly, MMb conferred better protection against Salmonella infection than HMb. A host-specific microbiota appears to be critical for a healthy immune system.
A field enquiry mentioned the potential positive impact of a feed restriction on the health of young rabbits, but no objective information relates the intake to digestive health. The effects of a post-weaning feed restriction strategy were thus studied on digestive health and growth and carcass parameters of the growing rabbit, using a monofactorial design that produces a quantitative linear reduction of the intake, from ad libitum (AL group) to 80%, 70% and 60% of AL. The study was performed simultaneously in six experimental sites, on 1984 growing rabbits (496 per treatment) collectively caged from weaning (34 to 38 days of age, depending on the site) to slaughter (68 to 72 days). The feeding programme was applied as followed: restriction during 21 days after weaning, and then ad libitum till slaughter. During the feed restriction period the growth rate was linearly reduced with the restriction level, by 0.5 g/day for each percent of intake reduction. When returning to ad libitum intake (after 54 days old) a compensatory growth and a higher feed efficiency occurred. Therefore, the impact of the feeding programme on the slaughter weight (SW) was significant (-4.5 g/% of restriction), but relatively moderate: the weight loss of the more-restricted rabbits (60%) reached 7.7% (-200 g) compared to the AL group. Over the whole fattening period, the feed restriction reduced linearly and significantly the feed conversion (FC) (-0.0077 unit/% of restriction). Carcass traits were little affected by the feeding programme, except for a slightly lower decrease of the dressing percentage (mean: 1.2 units between AL and the three restricted groups). On the six experimental sites, mortality and morbidity were always caused by acute digestive disorders, namely diarrhoea and/or caecal impaction. Independent of the treatment, the mortality rate strongly varied according to the site (between 7% and 18% from weaning to 54 days and for the AL group). During feed restriction, the mortality was significantly lower from a restriction threshold of 80% (meanly: -9% compared to AL). The morbidity was also significantly reduced (-6%) for the two most restricted groups (70% and 60%). The favourable effect of a lower intake on health did not persist after returning to ad libitum intake (54 days to slaughter), since mortality and morbidity were not significantly different among the treatments. Such a feeding strategy thus represents a double benefit in terms of feed costs and lower losses of young rabbits.
This work aimed to study the response of the growing rabbit caecal ecosystem (bacterial community and caecal environmental parameters) after a switch from a control to a low-fibre diet (LFD). A group of 160 rabbits were fed ad libitum a control diet (ADF: 20.4%) from weaning (36 days). At 49 days of age (day 0), 75 rabbits were switched to a LFD group (ADF: 10.7%), whereas 85 others (control group) remained on the control diet, for 39 days. Caecal contents were regularly sampled throughout the trial (60 rabbits per group). The bacterial community structure was characterized using CE-SSCP (capillary electrophoresis single strand conformation polymorphism) and total bacteria were quantified using real-time PCR. Redox potential (Eh), pH, NH(3)-N, volatile fatty acid (VFA) were measured in the caecum to characterize environmental parameters. The reduction of fibre in the diet modified the CE-SSCP profiles (P < 0.001) but not the diversity index (5.6 ± 0.8, ns). The number of 16S rRNA gene copies of total bacteria decreased (P < 0.01) in LFD rabbits compared with controls. In LFD rabbits, the caecal environment was less acid (+0.2 units; P < 0.01), more reductive (-11 mV; P < 0.05) and drier (+3.4 g 100 per g; P < 0.001), with an increase in NH3-N (+77%; P < 0.001) and a decrease in total VFA concentration (-17%; P < 0.001). We found significant correlations between the bacterial community, the quantity of bacteria and the caecal traits of the caecal ecosystem. Indeed, in both groups, the caecal traits barely constrained the total inertia of the CE-SSCP profile set (less than 14%), whereas total bacteria were positively related to total VFA, acetic acid and butyric acid levels, and Eh, and negatively related to pH. All the microbial and environmental modifications had occurred by day 2 and remained stable thereafter. These results suggest that the bacterial community in the growing rabbit caecum is able to adapt quickly after a change to in the dietary fibre supply to reach a new steady-state equilibrium.
This work aimed to study the stability over time of the bacterial community in caecum and faeces of the rabbit (diversity index and structure) without experimental disturbance and to evaluate its relationships with environmental parameters. Soft and hard faeces of 14 rabbits were sampled for 5 weeks while caecal content was sampled on the 3rd week (by surgery) and the 5th week (at slaughter). Bacterial communities were assessed by studying CE-SSCP profiles of 16S rRNA genes fragments. Redox potential, pH, NH3-N concentration and volatile fatty acid concentrations were measured in the caecum. Data showed that bacterial communities of soft and hard faeces barely differed from that of the caecum (ANOSIM-R<0.25; p<0.05). Without disturbance, the bacterial communities of faeces were stable over time (ANOSIM-R<0.25; p<0.001). However, the bacterial communities of caecum and faeces were affected by the surgery (ANOSIM-R=0.22-0.33; p<0.001). The caecal content was an acidic (pH=6.03+/-0.33) and an anaerobic environment (redox potential=-160+/-43 mV). Only the redox potential was correlated with the diversity index of the bacterial community of the caecum (R(2)=0.35; p<0.05) and no environmental parameters were correlated to its structure.
The diversity of bacteria present in the caecum of the rabbit was investigated. Partial bacterial 16S rRNA genes from a digested sample collected from the caecum of an adult rabbit were amplified by PCR. Sequence analysis of the amplified fragments indicated highest similarity was to bacterial sequences previously described from other gut environments. However, only one sequence showed significant identity (97% threshold) to any previously described bacterial 16S rRNA genes. Furthermore, most of the sequences clustered together in groups lacking representatives from sequences already described, suggesting that the rabbit caecal flora contains organisms not previously described.
Methane is the most important anthropogenic contribution to climate change after carbon dioxide and represents a loss of feed energy for the animal, mainly for herbivorous species. However, our knowledge about the ecology of Archaea, the microbial group responsible for methane synthesis in the gut, is very poor. Moreover, it is well known that hindgut fermentation differs from rumen fermentation. The composition of archaeal communities in fermentation compartments of goats and rabbits were investigated using DGGE to generate fingerprints of archaeal 16S rRNA gene. Ruminal contents and faeces from five Murciano-Granadina goats and caecal contents of five commercial White New Zealand rabbits were compared. Diversity profile of methanogenic archaea was carried out by PCR-DGGE. Quantification of methanogenic archaea and the abundance relative to bacteria was determined by real-time PCR. Methanogenic archaeal species were relatively constant across species. Dendrogram from DGGE of the methanogen community showed one cluster for goat samples with two sub-clusters by type of sample (ruminal and faeces). In a second cluster, samples from rabbit were grouped. No differences were found either in richness or Shannon index as diversity indexes. Although the primer sets used was developed to investigate rumen methanogenic archaeal community, primers specificity did not affect the assessment of rabbit methanogen community structure. Rumen content showed the highest number or methanogenic archaea (log10 9.36), followed by faeces (log10 8.52) and showing rabbit caecum the lower values (log10 5.52). DGGE profile showed that pre-gastric and hindgut fermenters hold a very different methanogen community. Rabbits hold a microbial community of similar complexity than that in ruminants but less abundant, which agrees with the type of fermentation profile.
The effect of the level of neutral detergent fibre (NDF: 0.35, LI and 0.42, HI) and neutral detergent soluble fibre (NDSF: 0.14, LS and 0.17, HS) in the caecal ecosystem was studied in 24 weaned (28 days of age) rabbits, weighing 630 ± 80.2 g in a 2 × 2 factorial design. After 22 days, rabbits were slaughtered and their caecal contents sampled. The caecal pH (on average 6.2) and molar volatile fatty acids (VFA) proportions were not affected by dietary treatments, but total VFA concentration tended to be lower with NDF (84.7 vs. 74.1 mmol/l; P = 0.095). The amount of total bacteria tended (P = 0.075) to increase with NDSF, but only in diets with 0.35 NDF. The caecal proportions of Ruminococcus albus and Fibrobacter succinogenes were not affected by type or level of fibre, but Butyrivibrio fibrisolvens decreased (P = 0.055) with the NDF proportion in LS diets. Denaturing gradient gel electrophoresis (DGGE) analysis showed that bacterial communities clustered according to each combination of NDF and NDSF, but did not greatly differ among diets (similarity indexes between 0.67 and 0.70), nor biodiversity was affected (average Shannon and richness indexes 3.50 and 33.1; P > 0.10). Archaeal population revealed changes in the amount and composition that were particularly evident in HS diets, decreasing in concentration (from 4.37 to 4.12 log(10) gene copy number/g) and biodiversity (Shannon index from 3.14 to 2.52 and richness index from 23.7 to 13.9) compared to LS. The type and level of dietary fibre had a minor impact on caecal fermentation traits or caecal bacterial community. However, the increase in NDSF from 0.14 to 0.17 reduced concentration and diversity of methanogenic archaea.
This study describes the development of the rabbit caecum microbiota and its metabolic activities from the neonatal (day 2) until the subadult period (day 70). The caecal microbiota was analysed using 16S rRNA gene approaches coupled with capillary electrophoresis single-stranded conformation polymorphism (CE-SSCP) and qPCR. At day 2, rabbits harboured population levels up to 8.4, 7.2 and 7.4 log(10) copy number g(-1) full caecum of the total bacteria, Bacteroides-Prevotella and Firmicutes groups, respectively. These populations reached their maximum levels from day 14 for Firmicutes groups (10.8 log(10) copy number g(-1) caecal content) and day 21 (11.4 and 10.7 log(10) copy number g(-1) caecal content of the total bacteria and the Bacteroides-Prevotella group, respectively). The archaeal population could be detected only from day 7 onwards (5.5 log(10) copy number g(-1) full caecum) and reached its maximum level at day 35 (7.4 log(10) copy number g(-1) caecal content). Similarity analysis, diversity calculation and quantitative evaluation of the stability of bacterial community CE-SSCP profiles provided some evidence that the caecal microbiota develops progressively from a simple and unstable community after birth into a complex and climax community in subadult rabbits. Meanwhile, the microbial activity evolved with the progressive decrease of the propionate/butyrate ratio towards a rabbit-specific value <1.
The mammalian intestinal mucosal surface is continuously exposed to a complex and dynamic community of microorganisms. These microbes establish symbiotic relationships with their hosts, making important contributions to metabolism and digestive efficiency. The intestinal epithelial surface is the primary interface between the vast microbiota and internal host tissues. Given the enormous numbers of enteric bacteria and the persistent threat of opportunistic invasion, it is crucial that mammalian hosts monitor and regulate microbial interactions with intestinal epithelial surfaces. Here we discuss recent insights into how the innate and adaptive arms of the immune system collaborate to maintain homeostasis at the luminal surface of the intestinal host-microbial interface. These findings are also yielding a better understanding of how symbiotic host-microbial relationships can break down in inflammatory bowel disease.
The consortia of microorganisms inhabiting the length of the gastrointestinal tract, the gastrointestinal microbiota, are vital to many aspects of normal host physiology. In addition, they are an active participant in the progression of many diseases, among them enteric infections. Healthy intestinal microbiota contribute to host resistance to infection through their involvement in the development of the host immune system and provision of colonization resistance. It is not surprising then that disruptions of the microbial community translate into alterations of host susceptibility to infection. Additionally, the process of the infection itself results in a disturbance to the microbiota. This disturbance is often mediated by the host inflammatory response, allowing the pathogen to benefit from the inflammation at the intestinal mucosa. Uncovering the mechanisms underlying the host-pathogen-microbiota interactions will facilitate our understanding of the infection process and promote design of more effective and focused prophylactic and therapeutic strategies.
The developmental changes of both pancreatic and intestinal enzymes and the influence of dietary composition on enzyme activities were followed in suckling and weaning rabbits. In addition, whole tract digestibility of nutrients was recorded in response to two dietary energetic sources. Rabbits were fed ad libitum either a low fat and high starch diet (group LF), or a high fat and high fibre diet (group HF) between d 32 and d 42, with both groups receiving a growing finishing diet thereafter. Before weaning (d 32) nutrient digestion was high (>75% for organic matter, protein or fat), and then decreased sharply, except for fat. Between d 32 and d 42, digestion in the HF group was 7.5 and 4.6% lower, respectively, for organic matter and protein, while fibre and fat digestion was higher (+14.0 and +5.0%, respectively). Between d 25 and d 42 of age, pancreatic-specific activities of trypsin and chymotrypsin did not change while those of amylase and lipase increased by 1.5- and 76- fold (P<0.05), respectively. However, total activities and relative activities expressed on a LW basis were increased after weaning as a main consequence of a specific increased organ weight and pancreatic protein content. Relative activities of trypsin and chymotrypsin increased by 63 and 56% (P<0.01) after weaning, respectively. Total activities of pancreatic enzymes measured in the total small intestinal contents increased during the same period, but the range of variations was lower than those measured in the pancreatic gland. Total activities of lipase, trypsin and chymotrypsin measured in the small intestine contents were significantly correlated with pancreas enzyme potentialities. Total small intestine activity of lipase was 58% higher (P<0.001) in HF than in LF group while the other pancreatic and intestinal enzyme activities measured were not influenced by the energetic sources of the diet. Decreased digestibility of organic matter and protein observed with the HF diet could not be related to changes in pancreatic or intestinal enzymatic profiles and may be more dependent on quality of dietary ingredients.
Mucosal surfaces are colonized by a diverse and dynamic microbiota. Much investigation has focused on bacterial colonization of the intestine, home to the vast majority of this microbiota. Experimental evidence has highlighted that these colonizing microbes are essential to host development and homeostasis, but less is known about host factors that may regulate the composition of this ecosystem. While evidence shows that IgA has a role in shaping this microbiota, it is likely that effector molecules of the innate immune system are also involved. One hypothesis is that gene-encoded antimicrobial peptides, key elements of innate immunity throughout nature, have an essential role in this regulation. These effector molecules characteristically have activity against a broad spectrum of bacteria and other microbes. At mucosal surfaces, antimicrobial peptides may affect the numbers and/or composition of the colonizing microbiota. In humans and other mammals, defensins are a predominant class of antimicrobial peptides. In the small intestine, Paneth cells (specialized secretory epithelial cells) produce high quantities of defensins and several other antibiotic peptides and proteins. Data from murine models indicate that Paneth cell defensins play a pivotal role in defense from food and water-borne pathogens in the intestinal lumen. Recent studies in humans provide evidence that reduced Paneth cell defensin expression may be a key pathogenic factor in ileal Crohn's disease, a subgroup of inflammatory bowel disease (IBD), and changes in the colonizing microbiota may mediate this pathogenic mechanism. It is also possible that low levels of Paneth cell defensins, characteristic of normal intestinal development, may predispose premature neonates to necrotizing enterocolitis (NEC) through similar close links with the composition of the intestinal microbiota. Future studies to further define mechanisms by which defensins and other host factors regulate the composition of the intestinal microbiota will likely provide new insights into intestinal homeostasis and new therapeutic strategies for inflammatory and infectious diseases of the bowel.