The small intestine of Burmese pythons, Python molurus bivittatus, undergoe
s a remarkable size increase shortly after feeding. We studied the dynamics
, reversibility and repeatability of organ size changes using noninvasive i
maging techniques. We employed light and electron microscopy, flow cytometr
y and immunohistology to study the cytological mechanisms that drive the si
ze changes of the small intestine. Within 2 days of feeding, the size of th
e small intestine increased to up to three times the fasting value. The siz
e changes were fully reversible and could be elicited repeatedly by feeding
. These enormous size changes were possible because the mucosal epithelium
of the small intestine is a transitional epithelium that allows for conside
rable size changes without cell proliferation. Histological evidence sugges
ted that a fluid pressure-pump system (lymphatic, blood pressure) was the d
riving force that inflated the intestinal villi. The rates of cell prolifer
ation were not elevated immediately after feeding but peaked 1 week later w
hen small intestine size was already declining. In contrast to the current
paradigm, we suggest that the small intestine is not part of the previously
proposed 'pay-before-pumping' model. Instead, the size of the python's sma
ll intestine may be upregulated without major metabolic investment. It can
occur even if the individual is energetically exhausted. An evolutionary pe
rspective of the transitional epithelium mechanism suggests superior functi
onality compared with the pay-before-pumping model because it allows for lo
ng periods of fasting and depletion of energy reserves, while still enablin
g the snake to digest prey and absorb nutrients.