The Immune System Development and Nutritional Requirements of Larval Fish

By: Dr. Terry Snell, Chief Science Advisor- Sustainable Nutrition Inc. 

Our sister company, Sustainable Aquatics Inc. operates a fish hatchery with over 120 recirculating aquatics systems (RAS) raising over 200 species of cold and warm water fish, including both marine ornamentals and Atlantic salmon.  Over the past 15 years, we have eliminated the use of antibiotics and vaccines by carefully replicating the micronutrients required for the optimal functioning of innate and adaptive immune systems that first emerged evolutionarily in jawed fishes and remains similar in both fish and humans 400M years later.

For fish to survive, its larvae must rapidly develop every tissue type needed to eat and avoid being eaten. Tremendous energy is allocated to developing eyes, jaws, liver and tail musculature.  However, fish also must fend off infection by bacteria, viruses and parasites. 1,2,3

Upon hatching, fish larvae depend on their innate immune system plus a set of enzymes transferred from their mother who retains signatures of the pathogens present in her rearing environment. This protects the larvae for the first 6 days or so until their thymus is developed in the thoracic cavity 4,5,6,7

The thymus is critical for the adaptive immune system to react to pathogens that are not in the immunological library passed from their mother 8,9,10. If infected by a new virus, the thymus is tasked with developing killer T-cells that can destroy cells infected by the virus. It also develops helper B-cells that train white blood B-cells how to develop the antibodies that neutralize the virus in the blood stream.

Avoiding predators and withstanding attacks by pathogens requires a tremendous amount of energy.  To protect their offspring, fish mothers pack up to 600K mitochondria into each egg cell 11,12,13. This high mitochondrial density has a downside because one of the by-products of energy production in cells is the production of reactive oxygen species (ROS) which are toxic to fish larvae.  During grow out, the mitochondria concentrations in tissues drop to 2-3000 per cell. 

One method of ROS mitigation comes from incorporating powerful antioxidants called carotenoids in cells, the most powerful of which is astaxanthin 14.  Astaxanthin is a powerful binder of ROS, thus protects the mitochondria and DNA from oxidative damage, as well as protects micronutrients critical for tissue development and metabolic function from being depleted by ROS.

Fish get astaxanthin from their diet by eating arthropods (krill, crustaceans, copepods e.g.) or other fish that ate arthropods.

Given this requirement for mitigating ROS during fish development, we recommend supplementing broodstock feeds  Amplifeed Topcoat beginning at three weeks or so prior to spawning at 5 parts commercial hatchery feed to 1-part Amplifeed Topcoat. 

For fish larvae initially fed live feeds, such as rotifers, we recommend feeding rotifers enriched with Amplifeed Replete two days before feeding to larvae. Amplifeed Replete is fortified with astaxanthin plus other micronutrients critical for first feeds.

When transitioning from live to dry feeds, we recommend supplementing the dry feed with Amplifeed Topcoat at 1 part Topcoat and 10 parts commercial hatchery diet until the completion of the allometric larval growth phase. 

To maintain good immune system health and growth rates, we recommend continued supplementation with astaxanthin enriched supplements but at reduced rates using  1 part Amplifeed Topcoat to 20-50 parts commercial hatchery feed. 

This feeding regimen has allowed us to eliminate loses from viral and bacterial infections and parasites, even though all of these pathogens are present in our water system.


1.  Ke Cui et al Development of immune functionality in larval and juvenile crimson snapper Lutjanus erythropterus 2018 Aquaculture Reports 10 (2018) 1–7

2. Olav Vadstein et al 2013 Microbiology and immunology of fish larvae Reviews in Aquaculture (2013) 5 (Suppl. 1), S1–S25

3 . Stephen A Renshaw and Philip W Ingham Zebrafish models of the immune response: taking it on the ChIn 2010 BMC Biology 2010, 8:148

4.  StefanChilmonczyk 1992 The thymus in fish: Development and possible function in the immune response Annual Review of Fish Diseases Volume 2, 1992, Pages 181-200

5.  T J Bowden1P CookJ H W M Rombout 2005 Development and function of the thymus in teleosts Fish Shellfish Immunol 2005 Nov;19(5):413-27.  doi: 10.1016/j.fsi.2005.02.003.

6.  Paolo Ronza 2020 The Teleost Thymus in Health and Disease: New Insights from Transcriptomic and Histopathological Analyses of Turbot, Scophthalmus maximus Biology 2020, 9, 221; doi:10.3390/biology9080221

7.  Jianmeng Cao 2017 Histology and ultrastructure of the thymus during development in tilapia, Oreochromis niloticus J. Anat. (2017) 230, pp720—733

8. E.Ellis 2005 Development of the immune response in relation to bacterial disease in the growing fish Biology of Growing Animals Volume 2, 2005, Pages 314-327

9.  Zhang Z, Chi H and Dalmo RA (2019) Trained Innate Immunity of Fish Is a Viable Approach in Larval Aquaculture. Front. Immunol. 10:42. doi: 10.3389/fimmu.2019.00042

10. Olav Vadstein 2013 Microbiology and immunology of fish larvaeReviews in Aquaculture(2013)5(Suppl. 1), S1–S25

11.  Yang Yan et al 2021 Dynamic changes in mitochondrial DNA, morphology, and fission during oogenesis of a seasonal-breeding teleost, Pampus argenteus Tissue Cell  2021 May 21;72:101558.  doi: 10.1016/j.tice.2021.101558.

12.  Szczepan M. Bilinski 2017 Selection of mitochondria in female germline cells: is Balbiani body implicated in this process? J Assist Reprod Genet (2017) 34:1405–1412

13.  Otten et al., 2016, Cell Reports 16, 622–630 July 19, 2016 ª 2016 The Authors.

14.  Suhn Hyung Kim and Hyeyoung Kim 2018 Inhibitory Effect of Astaxanthin on Oxidative Stress-Induced Mitochondrial Dysfunction-A Mini-Review Nutrients 2018, 10, 1137; doi:10.3390/nu10081137