Feeding polyamines to suckling piglets improves gut recovery after early weaning

Sunday, April 5, 2015

Research has found that use of polyamines, such as putrescine, and their precursors, such as proline, can improve epithelial restitution and barrier function after stress injury in early-weaned piglets

by JANICE MURPHY

Polyamines play an important role in cell growth, survival and proliferation. Three polyamines (putrescine, spermidine and spermine) are part of the very tightly regulated polyamine metabolic pathway. The three main sources of polyamines are through consumption, cellular synthesis and microbial synthesis in the gut.

Since newly weaned piglets are regularly exposed to stress, the ability to resist stress is an important part of their acclimatization to life beyond the farrowing room. Various studies of different organisms, including plants and animals, have shown that polyamines generally support stress resistance.

The intestine plays a crucial role not only in digestion and absorption of nutrients, but also in providing a barrier against harmful antigens, pathogens and toxins. At weaning, young piglets experience sudden changes that cause morphological and functional changes in the intestine, such as villous shortening and crypt elongation. There is also a coincidental reduction in the activity of digestive enzymes and nutritional transports, and often barrier function becomes compromised. Maintaining the barrier provided by the gastrointestinal epithelium is a complex process that is controlled by many key factors.

Polyamines are essential for normal integrity of the gastrointestinal epithelium. Previous research has shown that administration of polyamines resulted in an improvement in gut growth and maturation in suckling rats and neonatal piglets. Polyamines are also involved in the expression and function of intercellular junction proteins, making them pivotal in the regulation of intestinal epithelia cell restitution after injury. Restitution is a process that describes how disruptions in the mucosal lining of the gastrointestinal tract reseal through migration of the epithelial cells around the tear.

Based on the literature on this topic, researchers at the Chinese Academy of Sciences in Beijing and North Carolina State University in Raleigh, N.C. recently completed a study into the effects of oral administration of putrescine and proline during the suckling period on epithelial restitution after early weaning in piglets. Their hypothesis centred on the idea that polyamines improve mucosal growth and epithelial restitution in early-weaned piglets.

Eighteen neonatal piglets (Duroc × Landrace × Large Yorkshire) from three litters were assigned to three groups – oral administration with an equal volume of saline (control), putrescine (five milligrams per kilogram of body weight) and proline (25 milligrams per kilogram of body weight) twice daily from day 1 to weaning at day 14 of age – with plasma and intestinal samples taken three days post-weaning. This three-day window post-weaning was selected because the most severe impairment to the intestinal barrier has been observed in piglets at two to five days post-weaning.

Growth performance results, summarized in Table 1, showed that initial body weight was similar among the treatments. Administration of putrescine and proline significantly improved body weight at day 3 post-weaning and average daily gain of piglets compared with the control. Proline treatment also significantly decreased plasma lactate concentration.

In the jejunum of the piglets on the putrescine and proline treatments, the villi height were significantly greater than those observed in the control treatment, but there were no differences in crypt depth, the ratio of villus height to crypt depth or goblet cell number among the three treatments (Table 2).

Putrescine administration significantly decreased the lymphocyte number compared with the control treatment. In the ileum, oral administration with proline significantly increased villus height while putrescine increased goblet cell number. Although the result was not significant, putrescine treatment tended to increase the ratio of villus height to crypt depth in comparison with those on the control treatment.

Regardless of the source, gastrointestinal polyamines contribute significantly to the polyamine body pool and are essential in the maturation and mucosal integrity of the piglet's small intestine. In this experiment, putrescine (the precursor of spermine and spermidine) and proline (the major source of ornithine for intestinal polyamine synthesis in suckling neonates) were used to improve intestinal maturation of suckling piglets. This earlier maturation of the intestine, in turn, contributed to faster restitution after stress injury. The administration of putrescine and proline improved growth performance at day three post-weaning of piglets, which was supported with positive effects on villus height of small intestine in weaned piglets.

In agreement with the impact of polyamine administration on morphology, the percentage of proliferating cell nuclear antigen (PCNA) positive cells in jejunal mucosa was increased in response to putrescine and proline administration (data not shown). These results indicate that putrescine and proline encouraged proliferation of the epithelial cells, made possible due to the impact of polyamines on DNA synthesis. In addition, proline administration increased mucosal alkaline phosphatase (AKP) activity in the jejunum, which is positively correlated with villus height.

In addition to stimulating mucosal proliferation, putrescine and proline administration reduced intestinal permeability, mainly due to a decrease of the plasma lactate concentration and increase of the expression of tight junction proteins. Plasma lactate levels are negatively correlated with intestinal permeability and the adhesion of white blood cells. As such, damage to intestinal cells results in an increase in the level of diamine oxidase and lactate when intestinal permeability is compromised during weaning or other stress.

These findings indicate that polyamines, such as putrescine, and their precursors, such as proline, can improve mucosal proliferation, intestinal morphology, and maintain intestinal integrity in early-weaned piglets, thereby improving epithelial restitution and barrier function after stress injury. BP

Janice Murphy is a former Ontario agriculture ministry swine nutritionist who now lives and works in Prince Edward Island.

Sources:
J. Wang, G. R. Li, B. E. Tan, X. Xiong, X. F. Kong, D. F. Xiao, L. W. Xu, M. M. Wu, B. Huang, S. W. Kim, and Y. L. Yin. 2015. Oral administration of putrescine and proline during the suckling period improves epithelial restitution after early weaning in piglets. J Anim Sci, posted 01/19/2015; doi:10.2527/jas2014-8230.
N. Minois, D. Carmona-Gutierrez, and F. Madeo. 2011. Polyamines in aging and disease. AGING 3(8): 716-732.