Introduction
For decades, one of the most familiar explanations of rumen development in the young calf has been simple and appealing: the calf begins to eat starter, fermentable carbohydrate is fermented in the rumen, butyrate is produced, and butyrate stimulates development of the rumen epithelium. As the epithelium develops, it becomes increasingly capable of absorbing volatile fatty acids (VFA) and converting butyrate (C4) to ketone bodies, particularly beta-hydroxybutyrate (BHBA). Increasing blood BHBA is then often viewed as evidence that the calf is becoming a functional ruminant.
There is a great deal of truth in this explanation. Butyrate clearly affects rumen epithelial growth and function. The classic work of Sander et al. (1959) showed stimulatory effects of sodium butyrate and propionate on rumen mucosa in young calves, and later work has identified effects of butyrate on papillary growth, apoptosis, cell-cycle activity, VFA transporters, and intracellular pH regulation (Mentschel et al., 2001; Malhi et al., 2013; Niwińska et al., 2016). But a closer look at several older and newer studies suggests that the usual explanation may be incomplete. In particular, it may confuse two related, but different, processes: growth of the rumen epithelium and metabolic differentiation of the epithelial cell.
What do we mean by “rumen development”?
Rumen development is often treated as if it were a single process. It is not. Morphological development includes growth of the rumen, increased papillary size and absorptive surface, and changes in epithelial thickness and structure. Functional development includes the ability to absorb VFA, maintain intracellular acid-base balance, and metabolize absorbed substrates. Metabolic differentiation includes the shift from the metabolism of a preruminant epithelial cell toward the characteristic metabolism of mature rumen epithelium, including the ability to oxidize butyrate and produce BHBA and acetoacetate.
Butyrate can influence many of these processes. Increased ruminal butyrate has been associated with reduced apoptosis, more cells entering the DNA-synthesis phase of the cell cycle, increased cyclin D1 expression, and increased papillary growth. Butyrate also affects transport and homeostatic proteins such as MCT1, MCT4, Na+/H+ exchangers, and proton ATPases (Niwińska et al., 2016). These are biologically important effects. However, they do not necessarily mean that butyrate is the signal that initiates the underlying metabolic differentiation of the cell.
A clue from animals without normal rumen fermentation
The strongest challenge to the simple butyrate-driven model comes from experiments in lambs in which normal rumen fermentation was minimized. Giesecke et al. (1979) compared rumen epithelium from lambs given access to solid feed with epithelium from lambs maintained on milk. As expected, the milk-fed lambs had poorly developed rumen epithelium morphologically. Yet by 9 to 10 weeks of age, this “undeveloped” epithelium was fully capable of substantial ketogenesis when butyrate was supplied in vitro. More importantly, ketogenic capacity increased markedly with age even when stimulation by normal rumen fermentation products had been prevented.
The age response was striking. In milk-fed lambs, BHBA production from butyrate was relatively low at one week and at 3 to 4 weeks, but increased sharply by 9 to 10 weeks. The tissue had acquired the machinery to use butyrate even though the animal had not experienced the normal sequence of starter intake, fermentation, and sustained ruminal butyrate production. In other words, the substrate was not required for the tissue to become competent to metabolize that substrate.
Lane et al. (2002) reached a similar conclusion using gene expression. They followed expression of enzymes involved in ruminal ketogenesis, including HMG-CoA synthase, the rate-limiting step in ketone-body production. Expression increased with age in both conventionally reared and milk-fed lambs. In the milk-fed animals, HMG-CoA synthase expression remained low early in life, then increased dramatically around 42 to 49 days. By 84 days, expression of the ketogenic enzymes did not differ among dietary treatments. The authors concluded that VFA in the rumen were not required for the development of ketogenic capacity.
Perhaps the calf is preparing for C4
These observations suggest a different way to think about epithelial development. Instead of butyrate being the molecule that tells an otherwise immature epithelial cell to become a rumen epithelial cell, metabolic differentiation may be substantially ontogenetic. At a characteristic stage of postnatal development—roughly the 4- to 7-week period in these lamb studies—the epithelium begins turning on the enzymes and metabolic pathways needed for the mature rumen phenotype.
Functionally, the animal appears to be preparing the rumen for a substrate that will soon become abundant. The developmental program establishes the capacity to metabolize C4 before large amounts of C4 are necessarily present. When starter intake and rumen fermentation increase, butyrate arrives at an epithelium that is becoming able to absorb and metabolize it. Butyrate can then serve as fuel, a trophic factor, and a regulator of transport and cellular function. In this view, availability of butyrate is well timed to accelerate and reinforce development, but it may not be what starts the metabolic differentiation process.
This interpretation also explains why diet can still matter. Lane et al. observed evidence that diet influenced the timing of HMG-CoA synthase expression before about 42 days, even though the developmental program ultimately proceeded in milk-fed lambs. Thus, the most reasonable model may not be “age or butyrate.” It is an age-dependent developmental program that can be modified, accelerated, and functionally expressed by the ruminal environment.
Butyrate is still biologically important
None of this argues that starter intake or ruminal butyrate is unimportant. The distinction is between initiating differentiation and shaping the developing organ. Butyrate has repeatedly been shown to stimulate papillary growth and alter epithelial metabolism. The review by Niwińska et al. (2016) summarizes evidence that butyrate reduces apoptosis, accelerates the cell cycle, supports the energy demands of proliferating epithelial cells, and increases systems involved in VFA absorption and intracellular homeostasis. Those are exactly the adaptations required when fermentation becomes a major source of nutrients.
At the same time, not every experiment produces a simple butyrate response. In a calf study, Ceh (2019) found no clear treatment effects of orally dosed sodium butyrate on papillary area, BHBA, epithelial proliferation, or MCT1 and MCT4 abundance. There were important limitations, particularly uncertainty about delivery of the treatment to the rumen, so this is not evidence that butyrate has no effect. It is useful evidence, however, that simply supplying butyrate does not necessarily reproduce the entire developmental process.
More recent work also suggests that BHBA itself may participate in the signaling network rather than simply being an end product or blood marker. Zhuang et al. (2026) supplemented young goats with BHBA sodium and observed increased papilla height and width and changes in epithelial pathways related to lipid, amino acid, and energy metabolism. Interestingly, the major ruminal VFA concentrations were not different between treatments. BHBA supplementation also increased dry matter intake, so cause and effect cannot be separated cleanly, but the study reinforces the idea that rumen development involves interacting signals among metabolites, epithelium, intake, and the microbiome.
What does this mean for dry feed and weaning?
The practical message is not to stop emphasizing starter intake. A calf cannot be successfully weaned on ontogeny alone. Solid feed is required to establish a fermentative microbial ecosystem, produce VFA, expand rumen contents, stimulate absorptive and transport capacity, and provide enough nutrients to replace those previously supplied by milk. Dry feed provides the metabolic “work” that the developing rumen must learn to handle.
But the wording may matter. Rather than saying that dry feed intake causes rumen development because its fermentation produces butyrate, it may be more accurate to say that dry feed exposes a developmentally maturing rumen to the substrates and metabolic load that accelerate and complete its adaptation to ruminal digestion. Age establishes part of the capacity; fermentation provides the challenge and the substrate.
This distinction may also affect how we interpret BHBA. Blood BHBA reflects more than starter intake or ruminal butyrate production. It depends on butyrate availability, epithelial mass and absorptive capacity, the age-dependent expression of ketogenic enzymes, and use of ketones by peripheral tissues. Thus, BHBA is a useful indicator of the transition toward ruminant metabolism, but it should not be interpreted as a simple meter of how much dry feed has “developed” the rumen.
The bottom line
The traditional story—starter intake leads to fermentation, butyrate production, rumen development, and BHBA production—is directionally useful but probably too linear. Butyrate is an important fuel, trophic factor, and metabolic regulator. However, evidence from milk-fed lambs indicates that a major component of rumen epithelial metabolic differentiation occurs with age even in the absence of normal ruminal VFA exposure.
A better working model is that the young ruminant contains an intrinsic developmental program that prepares the rumen epithelium for the time when C4 and other fermentation products will become abundant. Starter intake and fermentation do not create that program; they interact with it, accelerate morphological and functional adaptation, and ultimately make the rumen capable of supporting the calf after weaning. That is a more complicated story than “butyrate develops the rumen,” but it may also be a more useful one.
References
Ceh, C. A. 2019. Environmental, Biochemical, and Dietary Factors that Influence Rumen Development in Dairy Calves. M.S. thesis, Virginia Polytechnic Institute and State University, Blacksburg, VA.
Giesecke, D., U. Beck, S. Wiesmayr, and M. Stangassinger. 1979. The effect of rumen epithelial development on metabolic activities and ketogenesis by the tissue in vitro. Comparative Biochemistry and Physiology Part B 62:459–463. https://doi.org/10.1016/0305-0491(79)90118-4.
Lane, M. A., R. L. Baldwin VI, and B. W. Jesse. 2002. Developmental changes in ketogenic enzyme gene expression during sheep rumen development. Journal of Animal Science 80:1538–1544.
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Malhi, M., H. Gui, L. Yao, J. R. Aschenbach, G. Gäbel, and Z. Shen. 2013. Increased papillae growth and enhanced short-chain fatty acid absorption in the rumen of goats are associated with transient increases in cyclin D1 expression after ruminal butyrate infusion. Journal of Dairy Science 96:7603–7616. https://doi.org/10.3168/jds.2013-6700.
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Niwińska, B., R. Klebaniuk, and K. Bilik. 2016. The role of butyric acid in the functional development of rumen epithelium in calves. Roczniki Naukowe Zootechniki 43(2):113–123.
Sander, E. G., R. G. Warner, H. N. Harrison, and J. K. Loosli. 1959. The stimulatory effect of sodium butyrate and sodium propionate on the development of rumen mucosa in the young calf. Journal of Dairy Science 42:1600–1605. https://doi.org/10.3168/jds.S0022-0302(59)90772-6.
Zhuang, Y., G. Liu, C. Jiang, M. M. Abdelsattar, Y. Fu, Y. Li, N. Zhang, and J. Chai. 2026. Dietary beta-hydroxybutyrate sodium alters rumen microbiome and nutrient metabolism in the rumen epithelium of young goats. Journal of Integrative Agriculture 25(4):1619–1635.
https://doi.org/10.1016/j.jia.2024.11.016.