Keywords

1 Introduction

The ancestors of domestic rabbits (Genus Oryctolagus) most likely evolved from the European rabbit, Oryctolagus cuniculus Linnaeus, 1758, in the middle Pleistocene period, which spread to nearby Mediterranean areas (Fox 1974; McNitt et al. 2013; Pelletier 2021). Although the first records of its association with humans go back to Romans, they were only considered truly domesticated approximately 200 years ago (Corbet 1986; Varga 2014). Despite all the years of domestication, rabbits still have a highly developed prey instinct (Sohn and Couto 2012) having evolved to be constantly vigilant, lightweight, and fast-moving, with a highly efficient digestive system (Meredith 2014).

The geographical distribution of rabbits was dramatically influenced by humans, since they were introduced in new areas, so that it could settle, reproduce, and become a food resource, for instance, on islands or shipping routes. Being highly adaptable animals, wherever they found suitable conditions, they established stable populations. Nevertheless, in some worldwide regions, such as North America, a significant diversity of rabbit species has developed instead of the relatively stable European rabbit (O. cuniculus) in Europe (Somerville and Sugiyama 2021). In other regions, such as Australia and New Zealand, they reproduced in such numbers that they became a pest, several decades after being introduced (Alves et al. 2022). The modern domesticated rabbit retains the main characteristics of the wild European rabbit, despite the differences in weight, color, coating, and behavior (Varga 2014).

Rabbits are classified as lagomorphs, and although they look like rodents in some morphological aspects, they differ in structural traits and serological data, showing more affinities with hoofed animals (Artiodactyla) (Nowak 1999). Modern lagomorphs are divided into two families, the family Leporidae, consisting of rabbits and hares, and the family Ochotonidae, which includes pikas (Meredith 2014). The family Leporidae includes many species that belong to eleven genera, Brachylagus, Lepus, Bunolagus, Caprolagus, Nesolagus, Oryctolagus, Pentalagus, Poelagus, Pronolagus, Romerolagus, and Sylvilagus (McNitt et al. 2013). The species Bunolagus monticularis, and Sylvilagus mansuetus are considered to be in a Critically Endangered situation (IUCN 2023), and others are considered to be   endangered species.

Some basic biological data is reported in Box 1.

Box 1 Basic Physiological Data for Rabbits. Adapted from Varga (2014) with Permission from Elsevier

  • Life span: 6–13 years

  • Rectal temperature: 38.5–40 °C (101.3–104 °F)

  • Heart rate: 130–325 bpm (beats per minute)

  • Respiratory rate: 32–60 bpm

  • Tidal volume: 20 ml (4–6 mL/kg)

  • Urine volume: 20–250 mL/kg/24 h (median: 130 mL/kg/24 h).

  • Blood volume: 55–65 mL/kg

  • Gastrointestinal transit time: 4–5 h

  • Optimum environmental temperature: 15–20 °C (65–70 °F)

  • Water intake: 50–100 mL/kg/24 h

This chapter aims to describe the fundamental particularities of rabbit physiology. Understanding the normal physiology of this species is essential for its successful management and disease prevention.

2 Behavior and Sensory Physiology

Wild European rabbits (O. cuniculus) are mainly nocturnal, gregarious, and live in groups of two to eight adults, plus juveniles (McBride 1988). In the group, there is a hierarchy, where older and larger males are dominant and defend the territory (Nowak 1999). Females dig burrows for protection and nesting (Lockley 1976). Frequently, these burrows are large and complex and can be 3 m deep and 45 m long (Nowak 1999). When males get older, they may be replaced in the hierarchy by younger, fitter males, becoming solitary (Lockley 1976). Although females are less aggressive than males, they defend their nest aggressively (Lockley 1976). Sexually active males may dispute territory, and in captivity, they must be kept separate. Injury, infertility, and pseudopregnancy can occur in animals housed in groups, especially if established after sexual maturity (McNitt et al. 2013).

Their territories, and members of the group, are marked by pheromones or by urine, especially by the males (Lockley 1976). They do this by using three specialized scent glands located in the chin, groin, and anal area (Mykytowycz 1968). Urine is also used for recognition purposes, and males spray it on females and young rabbits of their group. Additionally, females may attack their own young if they have been smeared with urine from other rabbits (Mykytowycz 1968). Rabbits defend themselves through bites and scratches with claws. Its agonistic behavior is characterized by hitting the hind limbs in a way to dissuade the adversary, as well as pursuit/combat, tail wagging, urinating, and squealing.

Many behavioral and physiological processes of rabbits show a marked diurnal rhythm (Crowell-Davis 2021). One example is feeding: wild rabbits are more active in the late afternoon. At this time, they emerge from their burrows to feed, socialize, explore their territory, and mate. The next morning, they return to the burrows (McBride 1988). Another example is the lagomorph characteristic behavior of cecotrophy. This behavior, which we will discuss later, is characterized by the ingestion of cecotrophs directly from the anus. These are soft capsules of cecal material rich in nutrients that are produced a few hours after feeding and during a quiet period of time (Varga 2014).

In nature, rabbits are prey animals, and their anatomy reflects this (Jenkins 2001). The visual field of rabbits is 190° for each eye (Hillyer 1994). This wide field of vision is possible because eyes are located laterally and on the top of the head. This positioning of the eyes allows them to detect any threat but makes it impossible for the animal to see what it is eating since it cannot see what is beneath their nose. As a consequence, food selection and ingestion depend on smell and tactile information received from the sensitive vibrissae of the nose and lips (Varga 2014).

Their sight in a dark place is good, but it is generally considered that rabbit color sense is poor (Vella and Donnelly 2012; Meredith 2014). Its retina consists of a double system of rods (recognizing luminosity) and cones (recognizing colors). Its pupillary dilation is wide, increasing its sensitivity (approximately 8 times more than that of humans) to light. In this way, they are very sensitive to the blue and green colors of twilight and have good nocturnal vision (Harkness et al. 2010).

Rabbits use their vibrissae and sensitivity of their lips, as well as smell and taste, during foraging (Meredith 2014). Vibrissae are also used during orientation in nests. Smell and taste are more important in identifying members of the own breeding group than vision (Morimoto 2009).

Their ears are conspicuous, with a large surface area, and rabbits’ ear sense is very good. Additionally, the ears are highly vascular and play an important role in thermoregulation (Meredith 2014).

3 Thermoregulation and Integument

Rabbits, as homeothermic animals, are able to keep their body temperature practically constant, between 38.5 and 39.5 °C, regardless of fluctuations in environmental temperature, within certain limits (Brewer and Cruise 1994). Nonetheless, they are extremely sensitive to heat (Batchelor 1999; Oladimeji et al. 2022). They do not sweat, and their salivation and panting are inefficient (O’Malley 2005). Only a few sweat glands are located inside the mouth (Yagci et al. 2006). Since they are unable to sweat or pant (Varga 2014), their thermoregulation depends largely on their ears, which have a countercurrent arteriovenous shunt: vasoconstriction or vasodilation occurs when the ambient temperature is lower or higher than the body temperature, respectively (Brewer and Cruise 1994).

When facing low ambient temperatures, the rabbit increases its food consumption and tries to reduce its body surface to decrease heat loss. In contrast, in the presence of excessive heat, the rabbit accelerates respiratory movements and evaporates water through the lung surface (O’Malley 2005).

High temperatures inhibit drinking, which can lead to dehydration. On the other hand, rabbits are sensitive to low humidity levels, but high humidity levels do not appear to be problematic (O’Malley 2005).

At birth, young rabbits (50–60 g) are hairless and have difficulty maintaining their body temperature since the mother just stays in the nest once, and only for a few minutes, to nurse them (Morimoto 2009). To maintain their body temperature and obtain a more favorable place to suckle, they huddle together (Hull and Hull 1982; McNitt et al. 2013). This behavior is complemented by heat production by metabolizing triglycerides in the brown adipose tissue (O’Malley 2005), a process used by newborn mammals to produce heat by nonshivering thermogenesis (Blumberg and Sokoloff 1998; Cannon and Nedergaard 2004; McNitt et al. 2013).

Rabbits exhibit three types of hair: undercoat (produced by the secondary hair follicles), long guard hairs (produced by the primary hair follicles), and short guard hairs, or awns (produced by the lateral primary hair follicles) (Cheeke 1987; O’Malley 2005). The differences in size, types, and color of hair produced the different rabbit breeds (O’Malley 2005). In a healthy animal, the different types of hair trap a layer of air close to the skin. This air layer rapidly warms, insulating the animal (Cheeke 1987; O’Malley 2005).

4 Respiratory Physiology

Rabbits are obligate nose breathers (Cruise and Nathan 1994; Meredith 2014). The entrance of each nostril is equipped with sensory pads, which makes rabbits very sensitive to touch on their nostrils (Nowak 1999). The nostril twitches at a very high rate, between 20 and 150/min, depending on the level of excitement (Brewer and Cruise 1994; Meredith 2014). This twitching will stop when the animal is very relaxed or anesthetized (Meredith 2014). The acute sense of smell of rabbits is explained by the vomeronasal organ and the olfactory epithelium in the turbinate bones (Brewer and Cruise 1994; Cruise and Nathan 1994; O’Malley 2005; Johnson-Delaney and Orosz 2011). As in other species, the airways harmonize the temperature and humidity of the inhaled air, filter any impurities it contains, and concomitantly intervene in the functions of smell and phonation.

At rest, rabbits mainly use the diaphragm contraction to breath (diaphragmatic breathing), not using their intercostal muscles (Brewer and Cruise 1994; Meredith 2014). The flow volume of air to the left lung is higher than that to the right due to the lower resistance of the proximal airways per unit volume (Yokoyama 1979). Additionally, lung volume increases with age in contrast to that of humans, in which it decreases (Morimoto 2009). Some respiratory parameters of rabbits are presented in Table 1.

Table 1 Respiratory parameters of rabbits. Adapted from Morimoto (2009) with permission from Springer Nature
Full size table

5 Cardiovascular Physiology

Heart rate can vary from 180 to 250 beats per minute (O’Malley 2005). In rabbits, the electric potential of electrocardiogram is low, and during surgery operation, some authors report arrhythmia, down of blood and pulse pressure (Harkness and Wagner 1995; Morimoto 2009). The rabbit heart is relatively resistant to oxidative damage (Matsuki et al. 1990), making it more resistant to stunning. Circulatory parameters and hematologic values are presented in Chapter “Insights into Clinical Pathology of Rabbits”.

The aorta exhibits rhythmic contractions of neurogenic origin, and the pulmonary artery is more muscular and thicker than that in cats or dogs (Meredith 2014). Additionally, the carotid artery of the rabbit is more compliant than that of the dog and has a greater ratio of elastin to collagen (Cox 1978). The external jugular vein is the main vessel for blood returning from the head (Meredith 2014).

Most likely because of its high metabolic rate, rabbit red blood cells have a short life span. Their neutrophils are called heterophils and stain pink (O’Malley 2005). Lymphocytes are the most prevalent leukocytes, reaching 60% (Harkness and Wagner 1995).

6 Urinary Physiology

Typical parameters of the urine of New Zealand White (NZW) rabbits are presented in Table 2.

Table 2 Urine parameters of New Zealand White rabbits. Adapted from Morimoto (2009) with permission from Springer Nature
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Rabbits need to drink, on average, 120 mL/kg body weight (BW)/day (Cheeke 1987; Harkness and Wagner 1995; O’Malley 2005). The water intake depends on the composition (moisture) and quantity of feed and ambient temperature (Brewer and Cruise 1994; O’Malley 2005).

Rabbit kidneys are unipapillate, and not all glomeruli are active at one time (Brewer and Cruise 1994; Cruise and Nathan 1994; O’Malley 2005). To activate dormant glomeruli, a well-hydrated rabbit does not need to increase renal plasma flow and glomerular filtration rate (Brewer and Cruise 1994; Cruise and Nathan 1994; O’Malley 2005).

One other characteristic is the lack of carbonic anhydrase, an enzyme that interconverts carbon dioxide and bicarbonate in other animals. This, together with the high production of bicarbonate by bacterial fermentation in the digestive system, makes rabbits more susceptible to metabolic alkalosis (Brewer and Cruise 1994; O’Malley 2005). Consequently, their urine is alkaline (Cheeke 1987; O’Malley 2005; Melillo 2007; Jenkins 2008).

Rabbits are also more susceptible to acid–base imbalance when bicarbonate levels are low. The reason for this is the lack of the renal ammonium buffering system: in other animals, in the case of metabolic acidosis, the ammonia levels are high, and the ammonia combines with hydrogen ions, which are then excreted as the buffer ammonium (Cheeke 1987; Brewer and Cruise 1994; O’Malley 2005).

The urine concentration ability of rabbits is lower than that of other animals, and consequently, they excrete large amounts of urine, approximately 130 mL/kg/day of urine (Mancinelli and Lord 2014). Urine volumes are affected by several factors, namely, individual and environmental factors. In some cases, traces of glucose and protein can be present (Jenkins 2008). Triple phosphate and calcium carbonate crystals are present in high numbers, but bacteria, epithelial cells and casts are absent in most cases (O’Malley 2005).

The main route for excretion of magnesium and calcium is the urine (Kennedy 1965). The high levels of ammonium phosphate and calcium carbonate monohydrate precipitates present explain its typical cloudy cream color (Flatt and Carpenter 1971; Morimoto 2009). Rabbits fed a 10% calcium carbonate diet excrete approximately 60% of the calcium carbonate in their urine (Cheeke and Amberg 1973). Urine color can vary from yellow to red (O’Malley 2005; Melillo 2007; Jenkins 2008) as a consequence of the presence of endogenous and exogenous pigments, such as bile pigments and plant porphyrins (Vella and Donnelly 2012; Meredith 2014), the latter depending on the ingestion of certain food items. For example, certain plant (beetroot, cabbage, broccoli, and dandelions) pigments can lead to the production of a bright red urine that can be confused with hemorrhage (Cheeke 1987; Melillo 2007; Jenkins 2008; Varga 2014). In young rabbits, however, urine is typically clear, although healthy young rabbits may have albuminuria (Morimoto 2009).

7 Reproductive Physiology

Rabbits reach sexual maturity by 4–4.5 months or at 4.5–5 months old in smaller and larger breeds, respectively (Batchelor 1999; Lebas 2000). Starting 48 hours after giving birth, the does exhibit a post-partum estrus, and the rabbit reproductive productivity can easily reach more than 60 kits per year (Lebas 1997).

In males, spermatogenesis begins between days 40 and 50 of life, but variation between breeds occurs (Morton et al. 1986; Lebas 1997). The testicular tubes are active from approximately day 84, and the first spermatozoa appear in the ejaculate at approximately 110 days (Lebas 1997).

The spermatogenesis duration is approximately 49 days, and spermatogenesis can produce 100–160 million spermatozoids daily (Foote and Carney 2000), with seasonal and genetic variations. Spermatozoid storage occurs in the epididymis (mainly in the tail) and ductus deferens, but their storage capacity is low, approximately 20 and 10% of the total, respectively (Orgebin-Crist 1965).

The volume of each ejaculate is approximately 0.3–0.6 ml. The concentration of spermatozoa in the ejaculate can vary from 150 to 500x106/ml, but volume and concentration can vary, depending mainly on the attempts made to copulate and the number of ejaculations per day (Lebas 1997).

In females, the first follicles appear in the ovary by the 13th day of age, and the first antrum follicles appear at approximately 65–70 days (Lebas 1997). The onset of puberty depends mainly on the breed and on body development. For most does, puberty arises when the female reaches 70–75% of its mature weight (Lebas 1997; Varga 2014).

After puberty, under the influence of FSH (follicle stimulating hormone), the ovarian follicles develop and produce estrogens, making the female receptive to the male. Follicular development takes place in waves of 5–10 follicles at the same time and at the same development stage in each ovary. If ovulation does not occur, these follicles regress, the estrogen levels diminish, and consequently, the female becomes less sexually receptive. After 4 days, the process is repeated (Varga 2014).

Rabbits are induced ovulators, and ovulation takes place 10–13 hours after coitus (Lebas 1997; O’Malley 2005; Varga 2014). The main reproductive events are reported in Table 3. In animal production, several methods can be used to induce ovulation without coitus, namely, mechanical manipulation of the vagina and administration of luteinizing hormone (LH) or gonadotropin releasing hormone (GnRH) (Lebas 1997).

Table 3 Main reproductive events
Full size table

Does can mate as early as 10–12 weeks of age, but normally this does not produce ovulation (Lebas 1997). The sexual behavior of a doe is different from that of most mammal females because it can stay in heat for many days, and a pregnant female may accept mating during pregnancy (Harkness and Wagner 1995; Lebas 1997). This behavior does not affect the pregnancy or the developing embryos, and there is no superfetation (two simultaneous pregnancies), as in hares (Lebas 1997; Varga 2014).

When ovulation occurs, the positioning of the oviduct pavilion is such that the liberated oocytes will enter in it. The sperm are deposited in the upper part of the vagina, and spermatozoa will reach the distal ampulla, near the isthmus, approximately 30 minutes later, and in the process, their fertilization capability is enabled (Lebas 1997).

The eggs reach the uterus approximately 72 hours after ovulation. Implantation takes place at the blastocyst stage in the uterine horns. Progesterone levels continuously rise from the third to 15th days after mating. After this, the levels stabilize and finally drop before parturition (Lebas 1997). The placenta develops with the fetus, becoming larger until parturition. Embryo losses during pregnancy occur in the last 15 days of pregnancy and are significant, eventually reaching 30–40% (Lebas 1997; O’Malley 2005). The reasons behind this are related to the viability of the embryos and their position in the uterine horns, the season of the year, and the physiological condition of the doe, especially its age (Lebas 1997). Gestational maintenance depends on the levels of progesterone, which is secreted by the corpora lutea (Varga 2014). The average gestation period is 31–32 days (O’Malley 2005; Elliott and Lord 2014; Varga 2014).

There is the possibility that unfertilized ova may produce a pseudopregnancy, lasting for 15–18 days. This condition is uncommon in natural mating production systems (Lebas 1997; Varga 2014) and can be caused by infertile mating or the presence of a nearby male (O’Malley 2005). In a pseudopregnancy, the uterus and mammary glands grow under the influence of progesterone secreted by the corpus luteum (O’Malley 2005).

At the end of gestation, under the influence of the secretion of prolactin and the increased ratio of estrogen versus progesterone, most does build a nest with the available materials (Lebas 1997). Does build their nest from hay, straw, or other bedding material and pluck fur from their dewlap, abdomen, and sides (Hrapkiewicz et al. 2013; Varga 2014). Apparently, corticosteroid secretion by the adrenal glands of the fetuses, as well as PGF2α prostaglandins, is involved in the onset of parturition (Lebas 1997; O’Malley 2005).

Parturition frequently occurs in the morning and takes between 15 and 30 minutes in most cases, depending on the litter size (Lebas 1997; O’Malley 2005; Varga 2014). After kindling, the uterus reduces its weight by more than half or less in 48 hours (Lebas 1997).

Kits are altricial, with their eyes closed and ear canals sealed, and weigh approximately 40–50 g (Harkness and Wagner 1995; Nowak 1999; Varga 2014). Other authors report a birthweight of approximately 65 g (Morimoto 2009). Kits are able to take solid food at approximately 20 days of age, and at approximately 4 weeks of age, they can leave the nest (Morimoto 2009).

During pregnancy, estrogen and progesterone inhibit the secretion of prolactin, but when kindling takes place, the levels of progesterone drop quickly. This change, together with the release of oxytocin, stimulates the secretion of prolactin, allowing for the amount of milk in the mammary glands. The stimulus of suckling leads to the release of oxytocin, the pressure in the mammary gland rises, and the kits can suckle. The amount of oxytocin released is directly related to litter size (Lebas 1997).

The doe nurses its litter once (Morimoto 2009; Varga 2014) or twice (Varga 2014) a day for 2–5 minutes each time. When being nursed, kits suck the equivalent of 20% of their bodyweight (Varga 2014). Doe’s milk is more concentrated than cow’s milk, except for lactose (O’Malley 2005; Varga 2014). The milk protein and fat levels increase after the third week of lactation, but the low level of lactose reaches near zero by the 30th day of lactation (Lebas 1997). Daily milk production goes from 30 to 50 grams at the beginning of lactation to 200 to 250 grams in the third week, dropping significantly afterwards (Lebas 1997).

8 The Digestive System and Digestion

The digestive system of the rabbit is ready to digest a large amount of fibrous food at a high transit rate (Varga 2014). Rabbits are extremely efficient herbivores, being capable of using fiber and protein in the diet with an efficiency 2.5–4 times that of other herbivores: p. ex., it can digest and absorb up to 80% of the protein present in the plant. If given a chance to choose, the rabbit prefers succulent and tender plants or parts of plants with a low content of fiber and high levels of protein and carbohydrates (Vella and Donnelly 2012).

8.1 Ingestion, Chewing, and Salivary Glands

The large visual field of rabbits does not include the area in front of the mouth (Brewer 2006). Food selection and ingestion are determined by smell from tactile information gathered from the sensitive vibrissae (tactile sensory organs that vibrate) on each side of the upper lip (Vennen and Mitchell 2009). This is an evolutionary adaptation of wild rabbits to remain visually alert (on the horizon) to potential predators. In the mouth, the first structures that process food are the teeth. Rabbit uses its incisor teeth to seize and cut (type I chewing action) shoots of young and succulent plants (in nature), a process that is facilitated by both the high mobility of the lips and the presence of a long diastema (Davies and Davies 2003).

The lower incisors occlude just behind the upper primary incisors, and the wearing between the upper and lower incisors forms a sharp edge and compensates for the continuous growth of the teeth. The incisors are used to cut through the vegetation. The ingested food is then ground by the molars and premolars before being swallowed (Brewer and Cruise 1994; Varga 2014).

After cutting, the plant is ground through the premolar and molar teeth present in each arcade functioning as a whole (type II action, the main one) and using only one of the two hemimandibles at a time. Type III actions are those involving the formation of a bolus of food. Up to approximately 120 jaw movements may occur after eating fresh food. When the cecotrophs are ingested, type II actions do not occur, and the cecotrophs are swallowed intact (Davies and Davies 2003).

During mastication, rabbits’ jaw movements are reported to be up to 120 per minute (O’Malley 2005). All the processes are accompanied by the continuous secretion of saliva, which contains amylase with activity similar to humans (Brewer 2006), but with a small quantity of lipase and urea (Davies and Davies 2003).

8.2 Stomach

After being swallowed, food passes to the stomach. The stomach itself represents approximately 15% of the volume of the gastrointestinal tract, and over 80% of the digesta are located in the stomach and cecum. In adult animals, the low pH of the stomach content (pH 1–2) sterilizes the ingesta before it passes to the small intestine (Varga 2014).

The fundic region of the stomach is the major secretory portion and presents low motor function, allowing the permanence of cecotrophs for 6–8 hours (Varga 2014). This permanence in the stomach allows bacterial fermentation within the cecotrophs, and by this time, the stomach pH rises to 3 due to the lactate buffer effect produced by these bacteria (Harcourt-Brown 2002b; Blas and Gidenne 2020).

The passage of the remaining material occurs for 3–6 hours. In this way, the stomach is always with content (feed and hair surrounded by fluid) that can reach 50% of food ingested 24 hours before (Kohles 2014).

In suckling rabbits, the stomach pH is higher, approximately 5–6.5, allowing for microbial inoculation of the hindgut. In these animals, the milk coagulates by enzymatic action similar to renin. The passage of this rennet to the intestine is slow, allowing a 24-hour suckling interval. Due to the action of an antibacterial “milk oil” (containing octanoic and decanoic acids), formed by the action of digestive enzymes on the doe’s milk, there is no bacterial proliferation, which does not happen if a substitute or milk from another species is given, making them very susceptible to infections (Davies and Davies 2003; O’Malley 2005).

Young rabbits depend exclusively on milk in the first 10 days of life, slowly starting to ingest solid/fibrous food by day 15. From day 20, the feeding is predominantly solid, initiating cecotrophy, which is fully developed on day 30. When young rabbits begin cecotrophy, the “milk oil” present in the stomach does not act on the cecotrophs since they remain intact and surrounded by mucus (mucin) (Davies and Davies 2003).

With the decrease in milk intake and weaning, the production of the antibacterial compound decreases, and simultaneously, the pH, that is, 5–6.5, descends to 1–2, forming a new barrier to bacterial growth (antibodies of maternal origin also decrease rapidly at this point). It is the transition between the different local defense mechanisms that leads to a lower protective capacity of the animal, contributing to the emergence of enteropathies such as weaning colibacillosis, coccidiosis, and mucoid enteritis, among others (Davies and Davies 2003).

8.3 Small Intestine

The rabbit has a rapid intestinal transit where the smaller fibrous particles are retained in the cecum for fermentation (Varga 2014). There are different processes of intestinal motility called segmentation and peristalsis (Box 2).

Box 2 Intestinal Motility Processes

  1. I.

    The segmentation, defined by periodic static contractions of the intestinal wall, with consequent mixing of the contents and with predominance in the duodenum.

  2. II.

    Peristalsis involves annular contraction with progression of the intestinal contents. It is regulated by cholecystokinin, somatostatin, and vasoactive intestinal peptide, among other substances.

Peristaltic contractions occur slowly every 10–15 minutes and are not altered by the cycle of cecotrophy (Davies and Davies 2003). The retention of chyme is approximately 10–20 minutes in the jejunum and 30–60 minutes in the ileum (Blas and Gidenne 2020; Carabaño et al. 2020). It is the motilin protein (as in humans and in contrast to other animal species) produced by enterochromaffin cells, one of the regulatory mechanisms of intestinal motility, that stimulates smooth muscle contraction by binding to specific receptors whose macrolide antibiotics are agonists. Its secretion is stimulated by fats and inhibited by the carbohydrates present in the intestinal contents. This regulation by motilin decreases gradually in the distal part of the small intestine, being absent in the cecum and reappearing in the large intestine and rectum (Davies and Davies 2003).

In the duodenum and jejunum, the simple carbohydrates and proteins of chyme are digested into monosaccharides and amino acids that are absorbed during their passage. This digestion includes the cecotrophs, which in this case are digested and therein are absorbed, namely, amino acids, volatile fatty acids, vitamins, and those derived from the digested bacteria. The lysis of these bacteria releases mainly amylase, which by itself also regulates the digestive process. However, the digestion of the protein of microbial origin intensifies with the addition of lysozyme in the colon (Davies and Davies 2003; Kohles 2014).

8.4 Large Intestine

Since the physiology of digestion in the stomach and small intestine of rabbits is similar to that of other monogastric mammals, the high digestion efficiency of the rabbit is explained by the large length of the digestive system and by the fact that it is a hindgut fermenter, relying on extensive microbial fermentation in the cecum for a significant nutrient supply (O’Malley 2005; Varga 2014).

In the hindgut, the separation of indigestible and potentially digestible matter takes place at the proximal colon, according to particle size. There, the large particles of indigestible fiber pass down the colon and are quickly eliminated as hard and dry fecal pellets. At the same place (proximal colon), small particles and fluid are directed to the cecum, where they are fermented. This fermentation is mainly of bacterial origin and releases volatile fatty acids (VFAs), microbial protein and vitamins (Varga 2014). VFAs are absorbed across the cecal epithelium and used as an energy source, accounting for up to 40% of the rabbits’ maintenance energy requirement. The VFA proportion in the rabbit cecum varies according to the time of day, diet, and rabbit developmental stage. Usually, VFA in cecum contents is 60% to 70% acetic, 15% to 20% butyric, and 10% to 15% propionic acid (Campbell-Ward 2012; Meredith 2014). Rabbits fed with low-fiber content and higher highly fermentable carbohydrate content have an increased appendix, showing their buffer function, or even evidencing the lymphoid tissue present there, due to the change in cecal population induced by this type of feeding (Davies and Davies 2003).

8.4.1 Cecal Microbiota

The cecal content corresponds to approximately 40% of the total content in the digestive tract (Brewer 2006). The cecum is the primary site of fermentation, and suitable cecal fermentation is only possible by the presence of large populations of bacteria (Crowley et al. 2017).

The cecum provides an anaerobic fermentation chamber for several bacteria with a diverse microbiota, such as Alistipes, Ruminococcus, Akkermansia, and Subdoligranulum (Bäuerl et al. 2014), and from the phyla Firmicutes (Velasco-Galilea et al. 2018) and Bacteroidetes (Montoro-Dasi et al. 2022). Nevertheless, as expected, feeding management or antibiotic use affects the cecal microbiota (Velasco-Galilea et al. 2020).

Lactobacillus and E. coli are usually absent but may be found in adult rabbits fed a high-carbohydrate, low-fiber diet (Varga 2014). Many nonpathogenic protozoan species, e.g., Entamoeba cuniculi, Eutrichomastix, Enteromonas, and Retortamonas spp., and yeasts are also present (Lelkes and Chang 1987; Owen 1992; Pakes and Gerrity 1994; Harkness and Wagner 1995).

The cecal microbiota breaks down, in a preferred order, ammonia (Fig. 1) (Xiao et al. 2015), urea, proteins, and enzymes from the small intestine and can also metabolize cellulose, xylan, and pectin (Carabaño et al. 2020). Substances that result from this metabolism are used as nutrients by microorganisms that use them to form their own protein and enzymatic structures, which will be subsequently digested as cecotrophs. The fermentation process also produces VFAs and vitamins, i.e. vit. B complex (e.g., niacin, riboflavin, pantothenate, cyanocobalamin), vit. C, and conversion of vit. K1 to K2.

Fig. 1
A cyclic chart illustration is as follows. Gut bacteria, N in cecotropes, N intake, and blood urea of dietary and endogeneous N, microbiota, bacterial protein synthesis, N H 3, and Feces.

Microbial nitrogen (N) recycling in growing rabbits. Modified from Xiao et al. (2015)

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8.4.2 Cecotrophy

The rabbit has the ability to produce two types of feces from the cecum: hard feces and soft feces called cecotrophs (Vennen and Mitchell 2009). Hard feces undergo a process similar to that of other herbivorous species, being well molded and excreted for the environment. Soft feces have different sizes, shapes, consistencies (higher water content), and odors than hard feces. At the chemical level, they also have a higher content of nitrogenous compounds, amino acids, and minerals, as well as the previously mentioned hydrosoluble vitamins, and a lower percentage of fibrous content when compared to hard feces (Carabaño et al. 1988; Fekete 1989).

Cecotrophs are produced primarily from fermentable material present in the cecal lumen and are partially fermented when adhered to the anus. Periodically, the fermented materials are excreted in the form of soft and moist cecal pellets, called cecotrophs, that are reingested by the animal directly from the anus. These reingested cecotrophs will be subjected to digestion a second time, and the nutrients released and produced in the fermentation process will pass through the small intestine and are absorbed (Varga 2014). The name of this behavior is cecotrophy.

Cecotrophs are produced approximately 4–8 h after feeding, and the behavior is exhibited during quiet periods, when the rabbit is in its burrow or in its cage (Harcourt-Brown 2002a, 2002b; Varga 2014). The production of cecotrophs varies inversely with the rabbit intake profile. When cecotrophy begins, ingestion ceases. Rabbits in cages and with normal photoperiods increase their intake between 15 and 17 h and remain elevated until 24 h. It decreases until 2 h in the morning, observing a new peak of intake at 6 h, which ends at 8 h. Thus, cecotrophy occurs between midnight and 2 h in the morning and returns at 8 h (Carabaño et al. 1988; Davies and Davies 2003; Carabaño et al. 2020).

Although the regulation of the daily profile of cecotrophy does not depend directly, for example, on satiety (the cyclic production of cecotrophs continues even if the animal does not eat food), cecotrophy is affected by energy and protein levels in the diet. If it is energy-deficient, a rabbit will consume all the cecotrophs produced (Meredith 2014). The intake of cecotrophs is most intense when rabbits are fed high levels of nondigestible fiber, whereas high protein levels reduce cecotrophy. Cecotrophs contain only approximately 50% of the crude fiber contained in hard feces. However, in situations of restriction of the protein level of feeding, cecotrophos maintain higher levels of protein compounds than hard feces (Davies and Davies 2003).

Cecotrophs are digested in the stomach and small intestine. The organization of the cecotroph, a soft pellet encapsulated in a gelatinous mucus coating, gives some protection from the low pH in the stomach while it is being stored in the fundic area (Harcourt-Brown 2002a; Fig. 2). Consequently, some fermentation occurs inside the pellet because of the bacteria present. These bacteria will be distributed by the lysozyme, secreted in the colon, and retained inside the cecotroph when it is formed, and its microbial protein will be available for further digestion and absorption in the small intestine, together with the amino acids and vitamins in the cecotroph (Varga 2014). Within the cecotroph, the amylase produced by the bacteria will digest carbohydrates, allowing for the degradation of glucose into carbon dioxide and lactic acid (Fekete 1989).

Fig. 2
A set of two schematics of the organs and components involved in the formation of hard feces pellets and caecotrophs with labeled parts such as H C O3, water, V F A, water, electrolytes, food water, vitamins, microbial amino acids, and others.

Formation of hard feces and cecotrophs (soft feces) in rabbit. Adapted from Harcourt-Brown (2002a) with permission from Elsevier

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8.4.3 Regulation of Cecotrophy and Feces Production

One of the main factors affecting transit time is hindgut motility (Ehrlein et al. 1983). The excretion of feces and cecotrophs exhibits a circadian rhythm: the hard feces formation phase coincides with feeding activity, followed by a cecotroph production phase (Fioramonti and Ruckebusch 1976; Ehrlein et al. 1983; Varga 2014; Carabaño et al. 2020).

While hard feces are being produced, water secretion into the proximal colon helps in the mixing and separation process. The cecum and colon motility separates the large indigestible particles and the small particle, bacteria and water soluble intestinal material. The first fraction is rapidly transported through the proximal colon, fusus coli and distal colon and is excreted as hard feces, and the second fraction is directed backward to the cecum (Varga 2014).

During the hard feces phase, the cecal motility is higher, particularly during the mixing and separation process in the colon. After this phase, the motility pattern changes, and the cecal material is moved along the large colon. In the fusus coli, the material is molded into small pellets encapsulated in mucus (see Fig. 2). Ultimately, these soft pellets are excreted: it is the cecotroph excretion phase. This excretion takes place at least four hours after the feeding period, particularly in rest periods (Varga 2014).

The shifts in motility depend on the fusus coli pacemaker activity (Pairet et al. 1986), and the nature and direction of the peristaltic waves change with the different excretion phases (Ruckebusch and Fioramonti 1976). This organ, and its action potential producing capability, is affected by hormones, namely, aldosterone and prostaglandins. Consequently, the motility patterns change: aldosterone levels are high during the hard feces production phase and low during the cecotroph production phase; in this last phase, under the influence of prostaglandins, proximal colon motility is inhibited, and distal colon motility is enhanced (Pairet et al. 1986). This motility pattern (low motility in the proximal colon and high motility in the distal colon) coincides with the elimination of cecotrophs (Varga 2014).

The low water content of hard feces is the consequence of the high water, potassium, and sodium loss of the fecal pellets when they pass through the fusus coli (Snipes et al. 1982) because of the compression of the intestinal contents as a result of the strong contractions of the muscle wall of this organ (Varga 2014). These materials pass to the distal colon, where they are absorbed, and the fibrous indigestible material is eliminated as dry fecal pellets.

9 Conclusions

Several physiological particularities of rabbits are strongly related to their adaptation to survive and reproduce in the environment, such as the diurnal rhythm of behavioral and physiological processes. This information assumes relevance for clinical approaches and animal welfare evaluations.

Cecotrophy is one of the most relevant particularities of lagomorphs, improving feed efficiency and maintaining cecal and intestinal microbiota. Nonetheless, some other specificities related to agonistic behavior (e.g., does aggressivity) and temperature control (i.e., heat stress) can also pose challenges for rearing rabbits. Knowledge of these physiological features is crucial to attempt to secure adequate responses at the homeostasis and homeorhesis levels.