Ingesta Retention Research Articles

New C3H KitN824K/WT cancer mouse model develops late-onset malignant mammary tumors with high penetrance

Gastro-intestinal stromal tumors and acute myeloid leukemia induced by activating stem cell factor receptor tyrosine kinase (KIT) mutations are highly malignant. Less clear is the role of KIT mutations in the context of breast cancer. Treatment success of KIT-induced cancers is still unsatisfactory because of primary or secondary resistance to therapy. Mouse models offer essential platforms for studies on molecular disease mechanisms in basic cancer research. In the course of the Munich N-ethyl-N-nitrosourea (ENU) mutagenesis program a mouse line with inherited polycythemia was established. It carries a base-pair exchange in the Kit gene leading to an amino acid exchange at position 824 in the activation loop of KIT. This KIT variant corresponds to the N822K mutation found in human cancers, which is associated with imatinib-resistance. C3H KitN824K/WT mice develop hyperplasia of interstitial cells of Cajal and retention of ingesta in the cecum. In contrast to previous Kit-mutant models, we observe a benign course of gastrointestinal pathology associated with prolonged survival. Female mutants develop mammary carcinomas at late onset and subsequent lung metastasis. The disease model complements existing oncology research platforms. It allows for addressing the role of KIT mutations in breast cancer and identifying genetic and environmental modifiers of disease progression.

Histopathological Changes of Transmissible Viral Proventriculitis in Broiler Flocks

Transmissible viral proventriculitis (TVP) is a poorly understood disease of broiler chickens. It is characterized by enlargement of the proventriculus, retention of ingesta in the lumen, and weakness of the gastric isthmus. Microscopically, degeneration and necrosis of the proventricular glandular epithelium is accompanied by marked lymphocytic infiltration. Samples from 13 chicken broiler farms from Romania, exhibiting clinical signs of TVP, poor feed conversion efficiency, and increased mortality have been examined by necropsy, histopathology (haematoxylin and eosin and Giemsa staining). The histopathological findings were dominated by the presence of enlarged, deformed glands, containing detritus with an inflammatory cell infiltrate composed of lymphocytes, histiocytes and surprisingly mast cells, as determined by special staining.

To chew or not to chew: fecal particle size in herbivorous reptiles and mammals

A major difference between reptile and mammalian herbivores is that the former do not masticate their food. Actually, food particle size reduction by chewing is usually considered one of the adaptations facilitating the higher metabolic rates of mammals. However, quantitative comparisons of ingesta particle size between the clades have, to our knowledge, not been performed so far. We measured mean fecal particle size (MPS) in 79 captive individuals of 14 reptile herbivore species (tortoises, lizards, and Corucia zebrata) by wet sieving and compared the results with a mammalian dataset. MPS increased with body mass in both clades, but at a significantly higher level in reptiles. Limited evidence in free-ranging and captive individuals of Testudo hermanni indicates that in reptiles, the ability to crop food and food particle size significantly influence fecal particle size. The opportunistic observation of a drastic particle size difference between stomach and intestinal contents corroborates findings that in reptiles, in contrast to terrestrial mammals, significant ingesta particle size reduction does occur in the gastrointestinal tract, most likely owing to microbial action during very long ingesta retention. Whether behavioral adaptations to controlling ingesta particle size, such as deliberate small bite sizes, are adaptive strategies in reptiles remains to be investigated.

Retention of fluid and particles in captive tapirs ( Tapirus sp.)

The retention of ingesta in the digestive tract is a major characteristic of herbivorous animals. We measured particle and fluid mean retention times (MRT) in 13 lowland tapirs ( Tapirus terrestris) and 5 Malayan tapirs ( Tapirus indicus) from five zoological institutions on their usual zoo diet and 2 lowland and 4 Malayan tapirs additionally on roughage-only diets (total n of trials = 24) with cobalt-EDTA as fluid and chromium-mordanted fibre (< 2 mm) as particle markers. MRT for fluid and particles averaged 42 ± 16 h and 55 ± 18 h in lowland and 40 ± 13 h and 56 ± 14 h in Malayan tapirs. In a General Linear Model, neither Tapir species, body mass or diet (characterised by the proportion of roughage) was significantly related to MRT, but dry matter intake was, with a steep decline in MRT with higher intake levels. Compared to other hindgut fermenters, tapirs have a low defecation frequency, which might be linked to their comparatively low food intake. Their gastrointestinal capacity (in dry matter: 1.63 ± 0.63% of body mass) is similar to that calculated for horses. A comparison of the difference in fluid and particle MRT in large hindgut fermenters (horses, rhinoceroses, elephants, and the tapirs of this study) shows that longer absolute particle MRT are linked to shorter relative fluid MRT, possibly indicating a more thorough ‘washing’ of particulate ingesta with digestive fluids at longer particle MRT. The only outlier to this general pattern, with an exceptionally high difference between fluid and particle MRT, indicating a particularly efficient ingesta washing, is the white rhinoceros ( Ceratotherium simum). If possible, results of this study should be compared to findings in tapirs on natural diets.

Evolutionary adaptations of ruminants and their potential relevance for modern production systems

Comparative physiology applies methods established in domestic animal science to a wider variety of species. This can lead to improved insight into evolutionary adaptations of domestic animals, by putting domestic species into a broader context. Examples include the variety of responses to seasonally fluctuating environments, different adaptations to heat and drought, and in particular adaptations to herbivory and various herbivore niches. Herbivores generally face the challenge that a high food intake compromises digestive efficiency (by reducing ingesta retention time and time available for selective feeding and for food comminution), and a variety of digestive strategies have evolved in response. Ruminants are very successful herbivores. They benefit from potential advantages of a forestomach without being constrained in their food intake as much as other foregut fermenters, because of their peculiar reticuloruminal sorting mechanism that retains food requiring further digestion but clears the forestomach of already digested material; the same mechanism also optimises food comminution. Wild ruminants vary widely in the degree to which their rumen contents ‘stratify’, with little stratification in ‘moose-type’ ruminants (which are mostly restricted to a browse niche) and a high degree of stratification into gas, particle and fluid layers in ‘cattle-type’ ruminants (which are more flexible as intermediate feeders and grazers). Yet all ruminants uniformly achieve efficient selective particle retention, suggesting that functions other than particle retention played an important role in the evolution of stratification-enhancing adaptations. One interesting emerging hypothesis is that the high fluid turnover observed in ‘cattle-type’ ruminants – which is a prerequisite for stratification – is an adaptation that not only leads to a shift of the sorting mechanism from the reticulum to the whole reticulo-rumen, but also optimises the harvest of microbial protein from the forestomach. Although potential benefits of this adaptation have not been quantified, the evidence for convergent evolution toward stratification suggests that they must be substantial. In modern production systems, the main way in which humans influence the efficiency of energy uptake is by manipulating diet quality. Selective breeding for conversion efficiency has resulted in notable differences between wild and domestic animals. With increased knowledge on the relevance of individual factors, that is fluid throughput through the reticulo-rumen, more specific selection parameters for breeding could be defined to increase productivity of domestic ruminants by continuing certain evolutionary trajectories.

Megaoesophagus in Rassf1a‐null mice

Megaoesophagus, or oesophageal achalasia, is a neuromuscular disorder characterized by an absence of peristalsis and flaccid dilatation of the oesophagus, resulting in the retention of ingesta in the dilated segment. The aetiology and pathogenesis of idiopathic (or primary) megaoesophagus are still poorly understood and very little is known about the genetic causes of megaoesophagus in humans. Attempts to develop animal models of this condition have been largely unsuccessful and although the ICRC/HiCri strain of mice spontaneously develop megaoesophagus, the underlying genetic cause remains unknown. In this report, we show that aged Rassf1a-null mice have an enhanced susceptibility to megaoesophagus compared with wild-type littermates (approximately 20%vs. approximately 2% incidence respectively; P = 0.01). Histological examination of the dilated oesophaguses shows a reduction in the numbers of nerve cells (both ganglia and nerve fibres) in the myenteric plexus of the dilated mid and lower oesophagus that was confirmed by S100 immunohistochemistry. There was also a chronic inflammatory infiltrate and subsequent fibrosis of the myenteric plexus and the muscle layers. These appearances closely mimic the gross and histopathological findings in human cases of megaoesophagus/achalasia, thus demonstrating that this is a representative mouse model of the disease. Thus, we have identified a genetic cause of the development of megaoesophagus/achalasia that could be screened for in patients, and may eventually facilitate the development of therapies that could prevent further progression of the disease once it is diagnosed at an early stage.

More efficient mastication allows increasing intake without compromising digestibility or necessitating a larger gut: Comparative feeding trials in banteng ( Bos javanicus) and pygmy hippopotamus ( Hexaprotodon liberiensis)

The digestion of plant material in mammalian herbivores basically depends on the chemical and structural composition of the diet, the mean particle size to which the forage is processed, and the ingesta retention time. These different factors can be influenced by the animal, and they can presumably compensate for each other. The pygmy hippopotamus, a non-ruminating foregut fermenter, has longer mean retention times than ruminants; however hippos do not achieve higher (fibre) digestibilities on comparable diets, which could be due to ineffective mastication. We performed feeding trials with six pygmy hippos ( Hexaprotodon liberiensis) and six banteng cattle ( Bos javanicus) on a grass diet. As predicted, both species achieved similar dry matter, organic matter, crude protein and gross energy digestibilities. However, neutral and acid detergent fibre digestibility was lower in pygmy hippos. Apparently, in these species, fibre digestibility was more influenced by particle size, which was larger in pygmy hippos compared to banteng, than by retention time. In spite of their higher relative food intake, the banteng in this study did not have greater relative gut fills than the hippos. Ruminants traditionally appear intake-limited when compared to equids, because feed particles above a certain size cannot leave the rumen. But when compared to nonruminating foregut fermenters, rumination seems to free foregut fermenters from an intrinsic food intake limitation. The higher energy intakes and metabolic rates in wild cattle compared to hippos could have life-history consequences, such as a higher relative reproductive rate.

In vitro digestibility of fern and gymnosperm foliage: implications for sauropod feeding ecology and diet selection

Sauropod dinosaurs, the dominant herbivores throughout the Jurassic, challenge general rules of large vertebrate herbivory. With body weights surpassing those of any other megaherbivore, they relied almost exclusively on pre-angiosperm plants such as gymnosperms, ferns and fern allies as food sources, plant groups that are generally believed to be of very low nutritional quality. However, the nutritive value of these taxa is virtually unknown, despite their importance in the reconstruction of the ecology of Mesozoic herbivores. Using a feed evaluation test for extant herbivores, we show that the energy content of horsetails and of certain conifers and ferns is at a level comparable to extant browse. Based on our experimental results, plants such as Equisetum, Araucaria, Ginkgo and Angiopteris would have formed a major part of sauropod diets, while cycads, tree ferns and podocarp conifers would have been poor sources of energy. Energy-rich but slow-fermenting Araucaria, which was globally distributed in the Jurassic, was probably targeted by giant, high-browsing sauropods with their presumably very long ingesta retention times. Our data make possible a more realistic calculation of the daily food intake of an individual sauropod and improve our understanding of how large herbivorous dinosaurs could have flourished in pre-angiosperm ecosystems.

An isthmus at the caecocolical junction is an anatomical feature of domestic and wild equids

The isthmus at the caecocolical junction in domestic equids is well described. Like another isthmus between the ansa proximalis coli (the colonic fermentation chamber or ‘large colon’) and the colon transversum (the distal or ‘small’ colon), this spot represents not only a potential anatomical feature contributing to particle ingesta retention but also an explicit predilection site for intestinal obstructions. The question whether this anatomical feature also occurs in wild equids is therefore of both physiological and medical interest but has not been addressed so far. In this paper, we report dissections of the large intestine of a domestic pony (Equus caballus f. dom.), a Przewalski horse (Equus przewalski) and a plains zebra (Equus burchelli). The intestinal tract section of all three animals were similar in length; each species displayed the caecocolical isthmus as well as the abrupt narrowing of the intestinal tract between the ‘large’ and the ‘small’ colon. Graphical descriptions of wild equid gastrointestinal anatomy should include these features.

Influence of two different diets on fluid and particle retention time Javan langur ( Trachypithecus auratus auratus)

In captivity, langurs (foregut fermenting primates) often suffer from digestive disorders, and in particular display soft stools on diets with a high proportion of fruits, vegetables, and grain products. In this study, we tested whether the improvement in feces consistency expected after an omission of vegetables from a conventional diet was also accompanied by a change in the excretion pattern as measured by the mean retention time (MRT). Two adult Javan langurs were kept together and offered a conventional diet of pellets, browse, vegetables, or a diet consisting of pellets and browse only. MRT were measured with cobalt-EDTA as the fluid and chromium oxide as the particle marker before, during, and after the test diet, collecting the feces of both animals together. MRTs of fluids and particles were longer (47/49 h) on the test diet as compared to the usual diet (42/43 h). Feces consistency improved during the test period. The test period was marked by an increased fiber intake; however, on the conventional diet, dietary water intake exceeded the calculated water flux for these animals distinctively, due to the high proportion of vegetables. Therefore, it cannot be decided whether the increase of fiber level alone or also a reduction of the excessive water intake was responsible for the changes observed. Comparing the results of this study to other studies on ingesta retention in foregut fermenting primates, no correlation between the body mass of the animals and the MRTs measured is evident, which is in accordance with observations in other groups of foregut fermenters.

Forage fermentation patterns and their implications for herbivore ingesta retention times

1 Differences in digestive physiology between browsing and grazing ruminant feeding types have been discussed extensively. The potentially underlying differences in fermentative behaviour of forage plants have received much less attention. 2 In this study, different groups of temperate forage plants (grasses, browse leaves and twigs, herbs and legumes) were compared in their chemical composition and fermentative behaviour. They were evaluated via an in vitro fermentation system (modified Hohenheim gas test), and relevant fermentation parameters such as maximal gas production and relative gas production rate were calculated. 3 Grasses generally had a higher NDF (neutral detergent fibre = total cell wall) content than browse leaves, herbs and legumes, while browse leaf cell wall was more lignified than that of herbs, legumes and grass. 4 With respect to fermentation parameters, grass had the highest maximal gas production, followed by herbs and legumes, and the lowest maximal gas production in browse leaves and twigs. Relative gas production rate was highest in herbs and legumes, while that of grass and browse was lower. As expected, browse twigs had the lowest nutritional value. 5 Dicot material reached given setpoints of absolute gas production rate like 1·0 or 0·5 mL gas/(200 mg dry matter × h) faster than grass material. Based on these results, a longer passage time of food particles seems to be adaptive for grazing ruminants, as over a wide range of fermentation times, absolute gas production rate is higher in grass compared with dicots. Especially for browse leaves, a higher intake level should be expected to balance energy requirements of animals relying on this forage type.

Digestion coefficients achieved by the black rhinoceros (Diceros bicornis), a large browsing hindgut fermenter

In contrast to the grazing white (C. simum) and Indian (R. unicornis) rhinoceros, the black rhinoceros (D. bicornis) is an exclusive browser. Due to the particular fermentation characteristics of browse, one would expect browsers to display both shorter ingesta retention times and lower digestion coefficients on comparable diets than grazers. In order to generate a database to test this hypothesis, we performed digestibility studies in eight black rhinoceroses (D. bicornis) from three zoological institutions, using total faecal collection for the quantification of faecal output. One to three regularly fed zoo rations of roughage, concentrates and varying proportions of browse material were used per animal. Additional data was taken from three hitherto unpublished studies as well as several published sources. When compared with horses on similar rations, black rhinoceroses achieved lower digestion coefficients for organic matter and CF. In general, an increase in dietary CF content led to a steeper decrease in organic matter and GE digestibility in black rhinoceroses than in horses. When comparing available data for rhinoceroses, browsing species showed a steeper decrease in organic matter digestibility than grazing species with increasing dietary cell wall content. Endogenous losses as determined by linear regression analysis were within the range reported for horses and Indian rhinoceroses. The results suggest that the horse is not a useful model animal for evaluating diets for black rhinoceroses energetically. In general, diets fed to captive black rhinoceroses seem to include higher proportions of concentrates than diets for other rhinoceros species, and an increase in browse or roughage would reduce digestion coefficients to levels observed in animals fed natural forage.

The dissociation of the fluid and particle phase in the forestomach as a physiological characteristic of large grazing ruminants: an evaluation of available, comparable ruminant passage data

Whether differences in digestive physiology exist between different ruminant feeding types has been an ongoing debate. In this regard, potential differences in ingesta retention have been understood to be of particular importance. We analyzed a data pool in which only mean retention time (MRT) data for the ruminoreticulum (RR) were collated that were obtained using comparable techniques with either chromium or cobalt EDTA as a fluid marker and/or with chromium-mordanted fiber of less than 2 mm in size as a particle marker. Data were compared using one averaged value per species. In general, the paucity of species in such a collection is striking and does not allow—in contrast to earlier statements—any final conclusions regarding the influence of body weight (BW) or feeding type on ruminant MRTs. In particular, there was no significant correlation between MRTparticlesRR or MRTfluidRR and BW, neither in the interspecific nor in the intraspecific comparisons, and no difference between the feeding types. The trend that indicates longer MRTparticlesRR in grazers is based on too few species to be conclusive. Small browsers seemed to have shorter MRTfluidRR than similar-sized grazers. In contrast, there was a trend for large grazers to have shorter MRTfluidRR than large browsers. In direct pair-wise comparisons between cattle and the browsers giraffe, moose, and okapi, the latter difference was significant. Cattle also had the highest relative RR fluid outflow rates among the species investigated. This is in accord with the observation that grazers have larger omasa, a major function of which is water-reabsorption distal to the RR. Grazers seem to have longer MRTparticlesRR per unit MRTfluidRR, and cattle are particular outliers in this respect. It is hypothesized that potentially shorter MRTfluidRR in large grazers and higher relative outflow rates are linked to a higher saliva production and a lesser viscosity of both saliva and RR fluids. A constant supply of a fluid phase of low viscosity is proposed to be the prerogative for the physical mechanisms of flotation and sedimentation that result in the stratification of RR contents and its selective particle retention typical for large grazing species.

Testing predictions on body mass and gut contents: dissection of an African elephant Loxodonta africana Blumenbach 1797

The values reported in the literature for the total gastrointestinal tract (GIT) content mass of elephants are lower than expected from interspecific mammalian regression. This finding agrees with theoretical considerations that elephants should have less capacious GITs than other herbivorous mammals, resulting in short ingesta retention times. However, the data on elephants was so far derived from either diseased zoo specimens or free-ranging animals subjected to an unknown hunting stress. In this study, we weighed the wet contents of the GIT segments of a captive African elephant that was euthanased because of a positive serological tuberculosis test, but that was clinically healthy, did not show a reduced appetite, and ingested food up to the time of euthanasia. The animal weighed 3,140 kg and its total gut contents were 542 kg or 17% of body mass. This is in close accord with the published mammalian herbivore regression equation of Parra (Comparison of foregut and hindgut fermentation in herbivores. In: Montgomery GG (ed) The ecology of arboreal folivores. Smithsonian Institution Press, Washington DC, pp205–230, 1978) and contradicts the notion that elephants have comparatively less capacious gastrointestinal tracts. Data on the individual gut segments, however, do support earlier suspicions that elephants have a comparatively less capacious caecum and a disproportionally capacious colon.

The digestive performance of mammalian herbivores: why big may not be that much better

ABSTRACT 1. A traditional approach to the nutritional ecology of herbivores is that larger animals can tolerate a diet of lesser quality due to a higher digestive efficiency bestowed on them by comparatively long ingesta retention times and lower relative energy requirements. 2. There are important physiological disadvantages that larger animals must compensate for, namely a lower gut surface : gut volume ratio, larger ingesta particle size and greater losses of faecal bacterial material due to more fermentation. Compensating adaptations could include an increased surface enlargement in larger animals, increased absorption rates per unit of gut surface, and increased gut motility to enhance mixing of ingesta. 3. A lower surface : volume ratio, particularly in sacciform forestomach structures, could be a reason for the fact that methane production is of significant scope mainly in large herbivores and not in small herbivores with comparably long retention times; in the latter, the substrate for methanogenesis – the volatile fatty acids – could be absorbed faster due to a more favourable gut surface : volume ratio. 4. Existing data suggest that in herbivores, an increase in fibre digestibility is not necessarily accompanied by an increase in overall apparent dry matter digestibility. This indicates a comparative decrease of the apparent digestibility of non‐fibre material, either due to a lesser utilization of non‐fibre substrate or an increased loss of endogenous/bacterial substance. Quantitative research on these mechanisms is warranted in order to evaluate whether an increase in body size represents a net increase of digestive efficiency or just a shift of digestive focus.

Intake, ingesta retention, particle size distribution and digestibility in the hippopotamidae

Although several aspects of the digestive physiology of the hippopotamidae—non-ruminating foregut fermenters—have been described, ingesta kinetics and passage characteristics of these species are not well understood. The most outstanding feature of the hippo digestive physiology reported so far is the very long mean ingesta retention times (MRTs) measured by Foose [Foose, T., 1982. Trophic strategies of ruminant versus nonruminant ungulates. PhD dissertation, University of Chicago, Chicago.]. Since those data had been investigated with animals without water access, we intended to measure MRT in hippos which were allowed to enter water pools during the night. MRT parameters as well as dry matter (DM) digestibility were determined in four common ( Hippopotamus amphibius) and four pygmy hippos ( Hexaprotodon liberiensis) on two different diets each using cobalt ethylendiamintetraacetate (Co-EDTA) as a fluid, chromium (Cr)-mordanted fibre (<2 mm) as a particle and acid detergent lignin (ADL) as an internal digestibility marker. Four of the animals additionally received cerium (Ce)-mordanted fibres (2–10 mm) as particle markers. Total MRTs for fluids and particles ranged between 20–35 and 48–106 h in the common and between 13–39 and 32–107 h in the pygmy hippos. The difference between fluid and particle retention was greater than usually reported in ruminants. Excretion patterns of the markers differed from those usually observed in ruminants but resembled those reported for macropods (kangaroos), indicating a plug-flow reactor-like physiology in the hippo forestomach (FRST). This finding complements other described similarities between the macropod and the hippo forestomach. The measurements of larger particle retention profiles suggest that in the hippo, larger particles might be excreted either faster or at the same rate as smaller particles, indicating a general difference between ruminants and hippos with respect to differential particle retention. The digestive physiology of hippos is characterised by a generally low food intake, long ingesta retention times and dry matter digestibilities lower than reported in ruminants. Moderate digestibilities in spite of long retention times might be the result of the generally high average ingesta particle size in hippos. The comparatively easy management of pygmy hippos, together with the significant correlations between food intake, MRT and digestibility in the pygmy hippos of this study, recommends this species for further studies on the interplay of these parameters in herbivore digestive physiology.

Impaired gastric emptying and altered intragastric meal distribution in diabetes mellitus related to autonomic neuropathy?

Previous studies in diabetic patients suggested a relationship between delayed gastric emptying and increased ingesta retention in either proximal or distal stomach, but the determinants underlying these abnormalities remained obscure. We aimed at assessing the impact of cardiovascular autonomic neuropathy, blood glucose concentration, long-term glycemic control, and other factors in 34 type I and 43 type II diabetic patients (ages 21-67 and 34-81 years, respectively). Emptying was slower (P < 0.04) in type I diabetic patients than in 20 healthy control subjects (ages 23-63 years). Patients with autonomic neuropathy (N = 45) had slower gastric emptying (P < 0.02) and retained more in the distal stomach (P < 0.0001) than patients without neuropathy (N = 32). Multiple regression analyses revealed that slow emptying and increased distal retention were significantly associated with autonomic neuropathy (P < 0.043, P < 0.0002), whereas blood glucose, glycemic control, diabetes duration, age, and other factors had no discernible influence. Thus, both slow emptying and increased distal ingesta retention seem primarily referable to autonomic neuropathy.

Modelling the nutritional ecology of ungulate herbivores: evolution of body size and competitive interactions.

A simulation model is used to quantify relationships between diet quality, digestive processes and body weight in ungulate herbivores. Retention time of food in the digestive tract is shown by regression to scale with W0.27, and to be longer in ruminants than in hindgut fermenters. Allometric relationships between whole gut mean retention time (MRT, h) and weight (W) were: MRT=9.4 W0.255 (r 2=0.80) for hindgut fermenters and MRT=15.3 W0.251 (r 2=0.76) in ruminants. Longer retention of ingesta by large-bodied ruminants and hindgut fermenters increases digestive efficiency relative to small animals and permits them to survive on lower-quality foods. Compared with ruminants, hindgut fermenters' faster throughput is an advantage which outweighs their lower digestive efficiency, particularly on poor quality foods, provided that food resources are not limiting. This suggests that the predominance of ruminants in the middle range of body weights results from their more efficient use of scarce resources under conditions of resource depletion. Considering only physical limitations on intake, the model shows that the allometric coefficient which scales energy intake to body mass is 0.88 in ruminants and 0.82 in hindgut fermenters. The advantages of large body size are countered by disadvantages where food quantity is limited, and we suggest that the upper limit to ungulate body size is determined by the ability to extract nutrients from feeding niches during the nadir of the seasonal cycle of resource quality and abundance.