Abstract
<b>Introduction</b>
Laparoscopic colorectal surgery and enhanced recovery programs have been
shown to improve patient outcomes and shorten length of stay following
surgery. There is growing evidence that perioperative supplementation with
immune-enhancing nutrition [IMN] containing Eicosapentaenoic acid [EPA]and
Docosahexaenoic acid [DHA] long chain, marine derived, omega-3 fatty acids can
further shorten length of stay, primarily by reducing infectious complications.
Their primary actions to achieve this include altering the lipid membrane
composition of peripheral blood mononuclear cells, and subsequently changing
the balance of inflammatory eicosanoids produced, which drive the innate
immune response. The aim of this study is to examine the effects of EPA and DHA
on the innate immune response, primarily measuring phagocytosis of pathogenic
bacteria.
<b>Methods</b>
A randomized controlled trial was conducted 2017-2019 (NCT03598413). All
patients underwent laparoscopic colorectal surgery for confirmed malignancy.
Patients were randomised 1:1 to receive a nutritional supplement containing
2.84g/day EPA and DHA or no supplementation. These were given for 7 days
pre- and 7 days post-operatively. Blood was taken pre-operatively, before
supplementation [Baseline], after 7 days of nutrition (on the day of surgery), and
day one post-operatively. The primary outcome was neutrophil and monocyte
phagocytosis of Staphylococcus aureus, Escherichia coli, and Mycobacterium
tuberculosis. Analysis of phagocytosis was via flow cytometry. Changes in the
fatty acid membrane composition of red [RBC] and white blood cells [WBC] were
analysed using Gas Chromatography Mass Spectroscopy.
<b>Results</b>
A total of 40 patients were recruited to the study with no dropouts, nor any lost
to follow up. Incorporation of EPA into RBC’s lipid membranes was significant
after 7 days of supplementation [Control (mean ± SD as % total phospholipids)
(1.28 ± 0.38 to 1.08 ± 0.42) vs. IMN (1.08 ± 0.49 to 2.94 ± 2.66) p=<0.05]. It was
also significant in PBMC’s [Control (mean ± SD as % total phospholipids) (0.53 ±
0.14 to 0.52 ± 0.14) vs. IMN (0.55 ± 0.19 to 0.79 ± 0.35) p=0.01]. There were no
differences in the primary outcome of phagocytosis between groups, for any
pathogen. There were significant correlations between phagocytosis and
membrane composition of Neutrophils with DHA [E.coli (Spearmans r=0.398,
p=0.012) S.aureus (Spearmans r=0.542 p=0.0004)] and with Monocytes for
Tuberculosis (Spearmans r= 0.363, p=0.021). Generally, increasing percentages
of EPA and DHA in PBMC correlated with an increased phagocytosis of all three
tested bacteria. In contrast however, increased levels of DHA in PBMC led to a
reduced phagocytosis of E.coli by both monocytes (Spearmans r= -0.463,
p=0.003) and neutrophils (Spearmans r = -0.330, p=0.04). Secondary outcomes
did not differ between groups.
<b>Conclusion</b>
There were no benefits observed in the supplemented group for the primary
outcome. There were significant changes with supplementation in lipid
membrane composition of both RBCs and PBMCs. Increased DHA in PBMC
enhanced the abilities of both monocytes and neutrophils to phagocytose
pathogenic bacteria. It is possible that the clinical effects may only be
appreciable when combination immunonutrition is used, or a targeted approach
to the clinically malnourished is adopted.