Most organisms on Earth have evolved to live in environments with low carbon dioxide (CO2) levels (Cummins et al., 2020). However, ruminants, which have a specialized foregut for fermentation, have adapted to live in environments with much higher CO2 concentrations (Turner and Hodgetts, 1955; Laporte-Uribe, 2023).

Several physiological adaptations allow ruminants to tolerate high CO2 concentrations in their forestomachs (rumen). These adaptations include:

1. Adult hemoglobin: Ruminant hemoglobin has a lower affinity for oxygen than hemoglobin in other mammals (Takano and Nishikura, 1976). This allows them to release oxygen more efficiently to their tissues, even in the presence of high CO2 levels (Ferguson and Roughton, 1934; Bunn, 1980).

2. Low levels of 2,3-diphosphoglycerate (DPG) in red blood cells (RBCs): DPG is an allosteric molecule that enhances the release of oxygen from hemoglobin. Ruminants have lower levels of DPG in their RBCs, which further facilitates oxygen release (Benesch et al., 1969; Gustin et al., 1997).

3. The chloride shift: The chloride shift is a mechanism by which bicarbonate (HCO3-) ions are transported across the RBC membrane. This helps to maintain the acid-base balance of the blood, which is important for CO2 transport and excretion (Westen and Prange, 2003; Kurbel, 2011).

4. Ruminal CO2 recycling: Ruminants preferentially use ruminal CO2 for nutrient absorption and recycling. This reduces the amount of CO2 that needs to be transported to the lungs for excretion (Whitelaw et al., 1972; Veenhuizen et al., 1988; Rackwitz and Gabel, 2018).

5. Increased saliva secretion: Under certain dietary conditions, ruminants increase their saliva secretion. This helps to buffer excess HCO3- in the blood and return it to the rumen (McDougall, 1948; Beauchemin et al., 2008; Ricci et al., 2021).

6. Urea formation, recycling, and disposal: Urea is a waste product that is formed by the combination of ammonia (NH3) and CO2. Ruminants have efficient mechanisms for urea formation, recycling, and disposal, which helps to reduce the accumulation of CO2 in their bodies (Thorlacius et al., 1971; Taylor and Curthoys, 2004; Abdoun et al., 2010; McCoard and Pacheco, 2023).

7. Cellular cholesterol deposition: The rumen has the highest intracellular cholesterol concentrations of the entire gastrointestinal tract (GIT). High intracellular cholesterol reduces CO2 transport across cell membranes, which helps to maintain a favorable acid-base balance (Arias-Hidalgo et al., 2018; Jiang and Loor, 2023).

8. Presence of the Glycoxylate shunt in the liver. The glyoxylate pathway is important for conditions like ketosis, acidosis, and negative energy balance (Soares et al., 2021). It is not found in mammal cells. In ruminants, it is considered a non-functional gene (Kondrashov et al., 2006). This pathway produce succinate and malate directly from acetyl-CoA, avoiding reactions in the TCA cycle that leads to CO2 production. For instance, Bacteria that use this pathway can still produce succinate even with high CO2 levels. When dCO2 levels are high, ruminal bacteria may use this pathway to increase propionate production. So, the presence of the glyoxylate pathway in ruminant liver’s under ketosis, NEB might indicate a direct link between those diseases and CO2 holdup.

The Significance of Ruminant Adaptations to High CO2 Levels

Ruminants have evolved remarkable adaptations to tolerate the high CO2 concentrations that arise from their specialized forestomach fermentation process. These adaptations enable them to thrive in environments that would otherwise be detrimental to their health.

The deposition of cholesterol in the rumen epithelium, for instance, serves to limit CO2 transport across cell membranes and maintain a favorable acid-base balance. This adaptation is crucial during the transition period, when ruminants must adjust to a diet with increased fermentable carbohydrates (Loor et al., 2006; Steele et al., 2011).

Monitoring ruminal dCO2 concentrations during this transition period will allow the proper adaptation to the new environmental conditions produced by production diets and avoid potential metabolic disorders such as subacute ruminal acidosis (SARA), ketosis, abomasal dysplasia and other metabolic syndromes associated with highly fermentable diets. By proactively addressing CO2 holdup and helping to sustain adequate ruminal dCO2 concentrations during transition, we can safeguard the health and productivity of ruminant animals by preventing many diseases associated to CO2 holdup.