Background

In this week’s deep dive, we will be looking at three topics: intestinal plasticity, hormones, and electron microscopy and EDX. First, we will discuss the definition of intestinal plasticity and its relation to the feeding habits of Burmese pythons. Second, we examine how hormones such as parathyroid hormone (PTH) and calcitonin regulate calcium and phosphorus levels in vertebrates. Third, we learn about electron microscopy and EDX (Energy-Dispersive X-ray) analysis and how these methods determine the elemental composition of biological samples.

Our first topic is about intestinal plasticity. Intestinal plasticity refers to the ability of an intestine to change its size, thickness, and cellular composition. In the Burmese python, the small intestine changes size, which is possible due to its mucosal epithelium. This function allows the intestine to regulate its absorption and secretion activity in response to external or internal signals. Due to the feeding habits of Burmese pythons, evolution has provided this adaptation. Said to be classic sit-and-wait predators, these pythons go through periods of fasting. When it is time to feed, they usually eat large meals. However, digesting these large meals takes a certain amount of energy. So, with intestinal plasticity, Burmese pythons can downregulate not only their gut mass but also its functions. Therefore, they minimize energy when fasting. When food becomes available, the reverse occurs, and the intestinal shape and function are upregulated to accommodate the digestion of prey. Burmese pythons can efficiently digest their food according to their feeding habits because of their intestinal plasticity.

The next topic discusses how parathyroid hormone (PTH) and calcitonin affect calcium and phosphorus levels in vertebrates. Calcium is crucial to vertebrates because it helps regulate processes including cellular signaling, protein and enzyme function, neurotransmission, and blood coagulation. Phosphorus is also important to vertebrates because it is a component of cell membranes and nucleic acids and participates in protein and enzyme function, cell signaling, and skeletal mineralization. To maintain homeostasis, PTH and calcitonin help regulate these minerals. For calcium, PTH increases calcium levels by stimulating bone resorption and absorbing calcium in the kidneys. Calcitonin decreases calcium levels by reducing bone resorption. For phosphorus, PTH decreases phosphorus levels by impeding renal phosphate absorption, while calcitonin slightly decreases phosphorus levels by limiting bone resorption and increasing renal excretion. PTH and calcitonin work together in a feedback system to balance calcium and phosphorus, ensuring stable levels for proper bodily functions.

Our last topic reveals what electron microscopy and EDX (energy-dispersive X-ray) analysis are and how they determine the elemental composition of biological samples. Both techniques provide high-resolution images of biological samples, but are used differently. Electron microscopy utilizes a beam of high-energy electrons to create an image with nanometer-scale resolution. Energy-dispersive X-ray (EDX) also utilizes an electron beam; however, the bombardment of this beam excites the atoms within a sample, causing the characteristic X-rays to be emitted. The use of an EDX detector measures the energy of the X-rays, providing qualitative and semi-quantitative scans of experimental analysis. Electron microscopy and energy-dispersive X-rays assist researchers and scientists in visualizing biological ultrastructure and elemental compositions, which is crucial in understanding how biological systems function at a molecular level.

Abstract

Studying the Burmese Python has revealed a potentially new specialized cell within its intestinal epithelium. This is possible because of the unique eating habits these animals possess. Burmese Pythons, along with lizards, Gila monsters, and other snakes, intake a high amount of calcium and phosphorus by digesting the whole skeleton or vertebrates of their prey. To understand how they process this high amount, small groups of 3-5 juvenile Burmese pythons were fed three different diets: an entire rodent with its bones providing calcium and phosphorus, a low-calcium diet from a boneless rodent, and a high-calcium diet from a rodent injected with calcium carbonate (CaCO3). The authors also studied snakes during fasting. Observation of the intestinal mucosa using light and electron microscopy techniques revealed the effects of these diets, leading to the discovery of a specialized cell involved in the snake’s production of calcium and phosphorus. Furthermore, we observe a difference in these snake cells when fed the three different diets, which provides insight into the processes a snake undergoes to absorb its meals.

New Cell Types Within the Burmese Python

As classic sit-and-wait predators, Burmese pythons go through periods of fasting from weeks to months. During this time, they can downregulate not only their gut mass but also its functions. Therefore, they minimize energy when fasting. Then, when food becomes available to them, the opposite occurs, and the intestinal shape and function are upregulated to accommodate the digestion of prey. We can observe this remodeling in the intestinal mucosa by its gastric luminal acidity, the release of pepsinogen, intestinal mass, microvilli length, intestinal nutrient uptake rates, and enzyme activity, as well as cellular replication along the mucosa (Lignot et al., 2025). As we dive deeper into the analysis of Python’s gut, we will discuss the differences between the three different diets of the snakes, regarding intestinal apical crypts, the crypt particles, their regulation of calcitonin levels, and whether the idea that these intestinal crypt cells are a new cell type is a good case.

Intestinal Crypts

First, there are the intestinal crypts of the fasting snakes. As previously stated in the introduction, the Burmese python can downregulate its gut function. The small depressions along the epithelial border are empty apical crypts containing short microvilli. Second, we look at the normal fed snake. These snakes consumed a whole rat with its bones and had a particle within its apical crypt. These particles came in varied sizes and structures, containing many nucleolar structures surrounded by layers of acellular elements, and possessed many vesicles. The microvilli of their crypts either remained unchanged or grew slightly. Third is the boneless diet snake. Their intestinal epithelium was similar to the normal fed snake, with microvilli demonstrating the same elongation. However, grainy electron-dense elements were in the apical crypts instead of a particle. The final observed is the snake with a calcium-rich diet. With no problems digesting their prey, inside their apical crypts was a multi-layered particle along with nucleation of electron-dense elements. Gathering this information, these particles are not left by their prey, but these cells are specifically produced by them to digest their bones (Lignot et al., 2025).

Structure of Crypt Particles
From these results, the two that had a particle within their crypts were the snakes with a normal diet and the snakes that consumed a calcium-rich diet. I would describe these particles as a spherical accumulation of minerals that appear when a snake has eaten a meal containing bones or considerable amounts of calcium. In both normal-fed and calcium-rich fed snakes, particles in their apical crypts were rich in mostly calcium and phosphorus; however, normal-fed snakes had notable amounts of sulfur and oxygen, while calcium-rich snakes presented iron in their particles and had a low amount of sulfur. Now, snakes with a boneless diet contain grainy electron-dense elements in their apical crypt. Without a high amount of calcium or phosphorus, we can see an abundance of iron, like the calcium-rich snake. Therefore, we can assume that iron must be within the crypts by these specialized cells before they can form these particles. Once formed, these particles can control the amount of calcium they consume (Lignot et al., 2025).

Controlling Blood Calcium
To study the amount of calcium that passes through, a blood analysis was performed on the pythons. The parathyroid hormone and calcitonin regulate calcium in the blood. When low, parathyroid hormone (PTH) activates to increase calcium by stimulating its release from bones and enhancing reabsorption in the intestines. If high, then calcitonin activates to decrease calcium by inhibiting osteoclast activity and increasing calcium excretion in the kidneys (Leko et al., 2021). Observing the fasted and normal-fed snakes, their blood calcium levels were relatively similar. However, looking at the pythons continuously fed a low-calcium diet (boneless prey), their blood calcium levels dropped after multiple feedings. As a result of this decrease, PTH levels increased, while calcitonin levels remained the same. Although not observed in the analysis, we can assume that during the high-calcium diet, calcitonin levels increased to decrease calcium. These mechanisms are crucial in regulating calcium levels, ensuring that pythons can function efficiently.

Is It New? With all the information provided, the authors made a good case that these intestinal crypt cells are new cell types. In summary, the Burmese python demonstrates an empty crypt cell during a fasting period. Then, once fed a calcium and phosphorus-rich diet, the cell produces particles of the same elements. If the python is not continuously consuming a diet with high levels of calcium, these particles do not form. This is evident in the snakes that fasted and fed a low-calcium diet. Furthermore, the authors stated that particles with similar structures and functions are found in other snakes and lizards, such as the Gila monster and boa constrictor. With further research, there is potential for the discovery of a new specialized cell.

References

Babić Leko, M., Pleić, N., Gunjača, I., & Zemunik, T. (2021). Environmental factors that affect parathyroid hormone and calcitonin levels. International Journal of Molecular Sciences, 23(1), 44. https://doi.org/10.3390/ijms23010044

Le Gall, M., Thenet, S., Aguanno, D., Jarry, A.-C., Genser, L., Ribeiro-Parenti, L., Joly, F., Ledoux, S., Bado, A., & Le Beyec, J. (2018). Intestinal plasticity in response to nutrition and gastrointestinal surgery. Nutrition Reviews, 77(3), 129–143. https://doi.org/10.1093/nutrit/nuy064

Leko, M. B., Pleić, N., Gunjača, I., & Zemunik, T. (2021). Environmental factors that affect parathyroid hormone and calcitonin levels. International Journal of Molecular Sciences, 23(1), 44. https://doi.org/10.3390/ijms23010044

Lignot, J., Pope, R. K., & Secor, S. M. (2025). Diet-dependent production of calcium- and phosphorus-rich ‘spheroids’ along the intestine of Burmese pythons: identification of a new cell type? Journal of Experimental Biology, 228(14). https://doi.org/10.1242/jeb.249620

Scotuzzi, M., Kuipers, J., Wensveen, D. I., de Boer, P., Hagen, K. W., Hoogenboom, J. P., & Giepmans, B. N. (2017). Multi-color electron microscopy by element-guided identification of cells, organelles and molecules. Scientific Reports, 7(1). https://doi.org/10.1038/srep45970

Secor, S. M. (2008). Digestive physiology of the burmese python: Broad regulation of integrated performance. Journal of Experimental Biology, 211(24), 3767–3774. https://doi.org/10.1242/jeb.023754
Shirley, B., & Jarochowska, E. (2022). Chemical characterisation is rough: The impact of topography and measurement parameters on energy-dispersive X-ray spectroscopy in Biominerals. Facies, 68(2). https://doi.org/10.1007/s10347-022-00645-4

Starck, J. M., & Beese, K. (2001). Structural flexibility of the intestine of Burmese python in response to feeding. Journal of Experimental Biology, 204(2), 325–335. https://doi.org/10.1242/jeb.204.2.325