According to a recent study performed by the University of Bologna it was found that the administration of nucleotides mix to suckling piglets and in the very early post-weaning phase is able to anticipate the maturation of the intestinal immunity and microbiota.

Nucleotides are considered essential for tissues that require rapid cell replication, among these are the intestinal epithelium and lymphoid cells, which have insufficient de novo synthesis of nucleotides. The presence of nucleotides in the diet to promote growth performance and the development of intestinal immunity and a healthy microbiota is therefore more important when animals are in stressful conditions or when they are in a transient malnutrition, such as at the time of weaning of the pig.

Nucleotides were therefore considered useful to mitigate the impact of weaning on the subsequent growth and health of the pig.

Up to now, many studies have been done on nucleotides benefits in post-weaning phase, but the peculiarity of this study is a focus on the combined effect of nucleotides administration to suckling piglets during the immediate post -weaning.

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Published on: Aug 26, 2020

Estratto da Dossier Alimentazione in “Rivista di Suinicoltura” n. 6 -Giugno 2020

“Secondo un recente studio condotto dall’Università di Bologna è stato rilevato che la somministrazione di una miscela di nucleotidi ai suinetti in fase di allattamento e nell’immediato post-svezzamento sia in grado di anticipare la maturazione del microbiota intestinale.”

La presenza di nucleotidi nella dieta per favorire le prestazioni di crescita e lo sviluppo dell’immunità intestinale e un sano microbiota è più importante quando gli animali sono in condizioni stressanti o quando sono in una transitoria malnutrizione, come al momento dello svezzamento del suino (Grimble e Westwood, 2001; Sauer et al., 2011). È tra l’altro nella fase tra l’allattamento e lo svezzamento che il suinetto soggiace frequentemente a delle patologie enteriche che possono avere esiti piuttosto devastanti e richiedono massicci interventi terapeutici con antibiotici. […]

Somministrazione di nucleotidi durante l’allattamento e nel post-svezzamento

«Curiosamente, mentre è già stato dato un certo rilievo agli studi riguardanti l’impiego di nucleotidi nella dieta di post-svezzamento (Sauer et al, 2012), non è invece stata considerata l’ipotesi di somministrazione durante l’allattamento. Si è quindi voluto valutare l’effetto combinato dell’apporto alimentare di nucleotidi in allattamento e nell’immediato post-svezzamento sulla crescita, sulla salute e sullo sviluppo dell’immunità intestinale e del microbiota nei suinetti».

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Prosol has been reported on Nutrition Insight about the use of dietary nucleotides for sports nutrition.

“The sports nutrition market is persevering despite the effects of COVID-19, with ingredient producer Prosol highlighting the role of dietary nucleotides in fighting fatigue, which can weaken the immune system.

Prosol notes that due to the accelerating pace of life and fierce social competition, fatigue has become a commonly occurring condition. However, fatigue is a suboptimal health status and may be associated with various illnesses. The Italy-based company details that repetitive and sustained physical labor results in fatigue, provoking systemic alterations, including endocrine, immune and metabolic dysfunctions.

Prosol also notes that several studies have found salivary immunoglobulin A (IgA) – an antibody that plays a role in mucosal immunity – to decrease following a bout of endurance exercise, such as cycling, cross country skiing, running and swimming, and also after shorter intense exercise.

However, Prosol states that dietary nucleotides, which are low-molecular-weight intracellular compounds, can help address many of these issues in sports nutrition by increasing salivary IgA and leading to faster recovery after performances. Additionally, the nucleotides can limit the inflammation process by lowering cortisol levels, neutrophils activation and muscle damage. An anti-fatigue effect can also be seen, with dietary nucleotides inhibiting oxidative stress and improving mitochondrial function in skeletal muscles.

Nucleotides participate in various biochemical processes and are composed of a nitrogenous base (pyrimidine or purine) linked to a pentose (ribose or deoxyribose) sugar to which one, two or three phosphate groups are attached.

According to Prosol, some cells with a high turn-over rate – such as those related to the brain, gut and immunity – are not able to produce enough nucleotides to cover their needs. Therefore, dietary nucleotides may be able to aid intestinal morphology and function, composition of intestinal microbiota, immune response, nervous system, as well as having the aforementioned anti-fatigue effect.”

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One of the greatest challenges in poultry nutrition is ensuring that broilers consume the quantity of nutrients necessary to ensure proper development and good weight gain. Nutrition can positively affect the performance of these poultry.

In particular, hydrolyzed yeast could be used as alternatives to antibiotics thanks to its positive effects on poultry performance even with strong nutritional challange.

I-CARE is a hydrolysed yeast from Kluyveromyces fragilis, which has positive effects on poultry performance thanks to high digestibility properties and presence of immune modulating components such as ꞵ-glucans and Mannan oligosaccharides.
Yeast cell wall fraction improves villus height (Zhang et al, 2005) and intestinal development of chicks, thus improving digestive capacity. Hydrolysis process leads to increase availability and digestibility of nutrients.

I-CARE increases feed conversion, growth performance and improves animal welfare right from the start to the end of the cycle. In particular, trials performed in 2019 have shown that Broilers treated with I – Care significantly improve FEED INTAKE and body weight gain.

Trial performed in 2019 with a strong nutritional challenge (high level of barley and oat without enzymes and coccidistats) have shown that broilers treated with I– Care keep high feed intake until the end of the trial.

I-CARE significantly improves FEED INTAKE (p<0.001) and numerically FCR.

Trial performed with a strong nutritional challenge (high level of barley and oat without enzymes and coccidistats) have shown that broilers treated with I – Care significantly improve BODY WEIGHT GAIN (p<0.001) all over the cycle.

BIOSPRINT® live yeast supplementation during the summer period helps lactating cows maintain their production parameters at optimum efficiency, preventing the negative effects of heat stress on their performance.

During the summer months, milk production can drop from 10% to 30%, which is an economic problem for milk producers (St. Pierre et al., 2003). The reduction in milk production is not due just to a reduction in dry matter intake induced by an increase in body temperature, but also to an alteration in the endocrine profile and energy metabolism (Baumgard and Rhoads, 2007), and to other factors that are still unknown (Collier et al., 2008).

It has been shown that, in lactating cows, the greater the milk production at the beginning of the heat wave, the greater the reduction in dry matter intake. The acceleration in the decline of dry matter intake in high-production animals is due to the need to rapidly decrease heat production in order to counteract the thermal overload. This means that the most productive dairy cows in the herd, the fresh cows, will be more likely to have a drop in feed intake, increasing the potential risk for the next lactation even in winter months (Collier et al., 2019). In addition, heat stress induces an increase in metabolic maintenance requirements of between 7% to 25% (NRC 2001).

To counteract heat stress, cattle implement physiological strategies that enable them to produce less heat and increase its dissipation (De Rensis and Scaramuzzi, 2003; West, 2003; Schutz et al., 2008).

Commonly seen strategies comprise:

Fig. 1: Rumination by cows decreases by 60 minutes per day for every 10 points increase in THI above the stress threshold (Mathew Haan, Penn State Extension, 2016).

From a behavioural point of view, the strategies implemented by the cattle are:

• a reduction in laying period and consequently less rumination (Fig. 1)
• an increase in water intake
• a reduction in feed intake frequency, with feeding concentrated in the coolest hours
• an increase in the amount of dry matter intake at every feeding visit

These physiological and behaviour responses increase the risks of rumen acidosis:

Indeed, it has been shown that the ruminal pH of heat-stressed cows when compared to thermo-neutral cows is lower both before (9.5% lower; P<0.01) and after (6% lower; P<0.05) the principal feeding (Gao et al. 2016).
In addition, it has been shown (Wheelock 2009) that 50% of the reduction in milk production is due to the drop in feed ingestion. In fact, during heat stress there is an alteration in energy metabolism with an increase in the use of glucose by cells. As a result, the availability of glucose for the synthesis of lactose, necessary for milk production, is lower. Therefore it is important to optimise rumen fermentation to ensure an adequate flow of amino acids and propionic acid in the blood. These substances are used by the liver to synthesise glucose, which is consequently insufficient in phases of stress.

Graph 1. Constant use of live yeast for a successful dairy farm

The reduced fiber intake in addition to increased risk of rumen acidosis, inevitably causes the depression of milk fat content. It has been shown that Biosprint® live yeast (MUCL™ 39885) is able to reduce the risk of acidosis and support milk production and quality.

In a test performed in a Turkish dairy farm with 880 Friesian cows under conditions of intense heat stress, Biosprint® live yeast (MUCL™ 39885) administered during the summer period improved fat content, while maintaining identical levels of production (Graph 1).

The benefits obtained by using live yeast remain constant and are consolidated if the yeast is used regularly and continuously, along all during the summer.

Only in this way “long-lasting” negative effects of heat stress can be prevented.
If the average performance of livestock farms is analysed, every year between July and August there is a drop of quantity and quality of milk produced (Graph 2). The return to optimum performance is achieved only in successive months, with a gradual improvement whose rate will depend on various factors specific to each individual herd.

In a herd consisting predominantly of animals with a long lactation period, it will be difficult to retrieve the milk lost during summer. The cows that calve in periods of greatest heat stress will tend to suffer an increase in the metabolic disorders typical of the post-partum period and will reach lower values of peak production. Moreover, by ingesting less dry matter, they will be more subject to a greater loss in weight, with negative impact on fertility. Negative effects will also be seen on cows in the dry period which, having spent the final part of pregnancy under the effects of heat stress, will show negative repercussions on mammary cell growth, with a consequent reduction in milk production during the imminent lactation and a delay in foetal growth with obvious limitations on genetic and productive potential (S. Thao and G. E. Dahl 2013).

Graph 3: The use of Biosprint® live yeast enables the group of primiparous cows to maintain optimum feed intake levels, with improved milk quality parameters.

It is therefore necessary to use both livestock management and nutritional preventive techniques in order to limit the negative effects of heat stress and to keep the herd’s performance at high levels of efficiency.

To show that nutritional strategies can help support the performance of cows during the summer months, last summer we tested feed intake and milk quality in a herd located in the province of Novara with 250 lactating cows. During the months of July and August, when temperature and humidity brought the THI to an average value of 76 and a peak value of 81, it was found that the constant use of Biosprint^® (5 g/cow/day) improved the cattle’s performance.

The group of primiparous cows who received Biosprint® MUCL™ 39885 for the entire summer period maintained an optimal feed intake and showed an improved fibre digestibility, as a result of the yeast’s beneficial effect on the cellulolytic flora, which in turn improved the milk’s fat content (Graph 3).

The group of pluriparous cows, which did not receive yeast for the entire month of July, suffered a notable drop in feed intake as temperatures increased. Only by adding rations of Biosprint^® to the feed was it possible to improve feed intake (Graph 4), production (+3.4 kg/cow/day) and milk fat content (Graph 5) for the pluriparous group as well.

The use of Biosprint® MUCL™ 39885 as a nutritional supplement has proved to be a good tool for helping cows to overcome the difficulties of the summer period, improving rumen efficiency and the herd’s productivity.

Nutrition is becoming more and more important for everybody, this is especially true when we are considering professional sportsmen, but also normal people. They take care of their diet to improve performances or just increase their wellbeing.

Furthermore, with an accelerating pace of life and fierce social competition, fatigue has become a commonly occurring condition. It is wise looking for new nutritional solutions to limit physical exercise consequences and to struggle against fatigue. Actually, fatigue is a suboptimal health status and may be associated with various illnesses.

Repetitive and sustained physical labor results in fatigue, provoking systemic alterations, including endocrine, immune, and metabolic dysfunctions:

– Immunity has been shown to be compromised in athletes, making them more susceptible to Upper Respiratory Tract Infections. Several studies have found salivary IgA to be decreased following bout of endurance exercise such as cycling, cross country skiing, running and swimming and also after shorter intense exercise (1, 2).

– Slight ischemia in the gut can damage mucosa and disrupt the mucosal barrier, resulting in increased permeability, and the resultant passage of pathogens, such as lipopolysaccharide, into the circulation (3,4).

– Cortisol level increases and it stimulates hepatic glucose release. Key signal for cortisol secretion is blood glucose decrease. Cortisol is also triggering an inflammation process through aspecific immune system as, for example, neutrophils degranulation.

– The innate immune system can also induce secondary muscle damage via the generation of reactive oxygen species (ROS), further attenuating athletic performance (5, 6).

– Excess of lactic acid is generated and accumulated in skeletal muscles, leading to muscle fatigue.

Upper Respiratory Tract Infections

A study, published in 2007, showed a positive effect of dietary supplements including RNA nucleotides on some immune system parameters post strenuous, high-intensity exercise. Dietary nucleotides significantly increased post supplementation period Salivary IgA, that is the major effector for defence against micro-organism causing Upper Respiratory Tract Infection and salivary cortisol, that is triggering an inflammation process through aspecific immune system (7).

Muscle Damages & Faster Recovery

The effect on cortisol is confirmed also in another trial performed in US, where a dietary supplement with nucleotides, was tested on resistance exercise stress and recovery, involving 20 people. Blood samples analysis collected after 15 and 30 minutes of an Acute Heavy Resistance Exercise Protocol (AHREP) showed a lower cortisol level against the control. The authors speculate that this effect may be due to the ability of dietary nucleotides to increase hepatic glucose output. Acting in this way the signal for the cortisol release disappears or it is reduced with all the related side effects. Another outstanding output was related to a marker of the muscles tissue damage: Creatine Kinase (CK) was significantly lower 24 hours after AHREP.
A lower CK value in nucleotide group means that muscle tissue damage was at a lower rate. Evidence, of what above mentioned, was that nucleotide group showed a faster recovery managing to finish AHREP already 24 hours after the first session, while control group managed to carry out all the physical protocol only after 48 hours (8).

Time to Exhaustion

A double-blind, placebo-controlled, randomized trial was conducted to assess the effect of sublingual dietary nucleotides as compared to placebo, both administered for 14 days in 30 healthy young male participants. Time to exhaustion, as well as serum immunoglobulin A and Natural Killer Cells cytotoxic activity, were significantly higher at day 14 (p < 0.05) in participants supplemented with nucleotides compared with those who consumed placebo. Once again dietary nucleotides improved some immunological and exercise performance indices (9).

Oxidative Stress Biomakers

In conclusion, dietary nucleotides exert these effects when used in sport nutrition:

–          Increasing Salivary IgA

–          Limiting the inflammation process:

o          Lower cortisol level

o          Lower Neutrophils activation

o          Lower Muscles damages

–          Faster recovery after performances

–          Ergogenic substances – Increase in time to exhaustion during running test

–          Anti-fatigue effect – Inhibition of oxidative stress and the improvement of mitochondrial             function in skeletal muscles (↑ ATP for energy supplementation)

Nucleotides are low-molecular-weight intracellular compounds that participate in numerous biochemical processes. They are composed of a nitrogenous base (pyrimidine or purine) linked to a pentose (ribose or deoxyribose) sugar to which one, two or three phosphate groups are attached.

De-novo synthesis does not satisfy the Nucleotides requirements of many tissues and particular life physiological phases, making necessary a reinforcement by dietary source. Particularly, some cells at high turn-over rate, such as gut, immune system and cerebral ones (lymphocytes, erythrocytes, bone marrow cells, glial cells) are not able to produce enough Nucleotides to cover their needs.

There is increasing evidence that dietary nucleotides may affect different aspects of body function and health in single-stomached animals, including:

• Intestinal morphology and function
• Immune response
• Composition of the intestinal microbiota
• Nervous system
• Anti-fatigue effect

1. Douglas DJ, Hanson PG. Upper respiratory infections in the conditioned athlete. Med Sci Sports Exerc 1978;10:55-60.
2. Mackinon LT, Chick TW et al. Decreases secretory immunoglobulins following intense endurance exercise. Sports Training Med Rehabil 1989; 1:209-18
3. Bosenberg AT, Brock-Utne JG et al. Strenuous exercise causes systemic endotoxemia. Journal of applied physiology 65: 106-108, 1988
4. Lamprecht M and Frauwallner A. Exercise, intestinal barrier dysfunction a probiotic supplementation. Medicine and sport science 59: 47-56, 2012.
5. Aoi W, Naito Y, et al. Oxidative stress and delayed-onset muscle damage after exercise. Free radical biology & medicine 37: 480-487, 2004
6. Close GL, Ashton T, et al. The emerging role of free radicals in delayed onset muscle soreness and contraction-induced muscle injury. Comparative biochemistry and physiology Part A, Molecular & integrative physiology 142: 257-266, 2005
7. Mc Naughton L, Bentley D et al. The effect of a nucleotide supplement on the immune and metabolic response to short term, high intensity exercise performance in trained male subjects. J Sports Med Phys Fitness 2007;47:112-8.
8. Sterzcala AJ, DuPont WH et al. The Physiological Effects of Nucleotide Supplementation on Resistance
   Exercise Stress in Men and Women J of Strenght and Conditioning Research 2016;
9. Ostojic SM, Idrizovic K et al. Sublingual Nucleotides Prolong Run Time to Exhaustion in Young Physically Active Men 2013; 5 4776-4785.
10. Xu M, Liang R et al. Anti-fatigue effects of dietary nucleotides in mice. Food & Nutrition Research 2017 Vol 61