beneficial effect of 6 months of probiotics on ... · gabriella di girolamo1, giancarlo...
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Abstract n. 419
BENEFICIAL EFFECT OF 6 MONTHS OF PROBIOTICS ON ASYMPTOMATIC NEUROCOGNITIVE IMPAIRMENT
Luigi Celani1, Eugenio N Cavallari1, Mariangela Fratino1, Claudia Pinacchio1, Giuseppe Corano-Scheri1, Gabriella Di Girolamo1, Giancarlo Ceccarelli1, Claudio M. Mastroianni1, Carolina Scagnolari1,
Vincenzo Vullo1, Gabriella d'Ettorre1.1“Sapienza” University of Rome
Presenting author: Luigi Celani
Session: Neuropsychological complications of
HIV infection – P-E2
Date: Mon, 3/5/2018
Time: 2:30 PM – 3:30 PM
Corresponding author: Luigi CelaniDepartment of Public Health and Infectious Diseases“Sapienza” University of Rome
BACKGROUNDHIV infected subjects show high prevalence of mild neurocognitive symptoms; individuals withAsymptomatic Neurocognitive Impairment (ANI) show increased risk of future symptomatic decline but todate interventional strategies to prevent the onset of symptomatic conditions have not been defined.Wider evidence shows that changes in the qualitative and quantitative composition of the gut’smicrobiome can affect the modulation of the gut-brain axis, thus resulting in the onset of behavioral andneurocognitive alterations.For these reasons, the use of probiotics represents a novel potential approach to manage conditions, andto ameliorate cognitive function in several pathological settings.
METHODS
35 HIV infected individuals successfully treated withHAART were enrolled in this unblinded, non-randomized study. At baseline (T0) a battery of 20neurocognitive tests was administered to evaluatepatients’ cognitive function and a lumbar puncturewas performed to determine neopterin concentrationin cerebrospinal fluid (CSF). Subsequently, 9participants underwent a 6 months course ofantiretroviral therapy supplementation with acommercially available oral probiotic (2 sachets, eachcontaining 450x109 billion bacteria, twice a day,available in USA as Visbiome® in Europe as Vivomixx® conteinig: Lactobacillus plantarum, Streptococcusthermophilus, Bifidobacterium breve, Lactobacillus paracasei, Lactobacillus delbrueckii subsp. bulgaricus,Lactobacillus acidophilus, Bifidobacterium longum, Bifidobacterium infantis); after supplementation,participants included in the interventional group were evaluated with a second lumbar puncture and with asecond neurocognitive tests assay, whereas controls underwent a second battery of neurocognitive testsafter 12 months (T12).
RESULTSAt T0 demographics, variables related to infection and neurocognitive tests results were similar betweenthe two groups; all participants showed an abnormal result in at least one test exploring the executivefunctions and most individuals presented a pathological impairment in at least two different domains;neopterin concentration in CSF was elevated in 33 out of 35 patients and a higher neopterin level wascorrelated with a poorer result in several neurocognitive tests. After supplementation with probiotics (T6),participants in the interventional group presented a significant decrease of neopterin concentration (p<0.005) and a significant improvement in many neurocognitive tests, while no significant modificationswere observed between T0 and T12 in controls.
CONCLUSIONS
Supplementation with this specific probiotic could represent a useful strategy to ameliorate cognitivefunction in HIV infected individuals with ANI. Further investigations are needed to define the long termbenefits of supplementation with this product.
Neurocognitivetests
Probioticssupplementationgroup
vs.Controlgroup(T6vs.T12)
Probioticssupplementationgroup(T0vs.T6)
Controlgroup
(T0vs.T12)
Rey-OsterriethComplexFigureimmediaterecall(moreisbetter)
22.0(19.0-23.7)vs.14.7(8.8-20.3)(p0.011)
16.6vs.22.0(p0.007)
13.1vs.14.7(p0.603)
Rey-OsterriethComplexFiguredelayedrecall(moreisbetter)
22.4(22.0-25.5)vs.12.6(5.7-19.1)(p0.011)
15.5vs.22.4(p0.008)
11.6vs.12.6(p0.369)
ReyAuditoryVerbalLearningTestimmediaterecall(moreisbetter)
53.0(49.3-55.6)vs.32.5(28.7-37.5)(p0.008)
46.0vs.53.0(p0.028)
30.6vs.32.5(p0.619)
ReyAuditoryVerbalLearningTestdelayedrecall(moreisbetter)
12.0(10.7-13.8)vs.5.3(4.3-8.0)(p0.008)
9.2vs.12.0(p0.034)
5.2vs.5.3(p0.241)
ReyAuditoryVerbalLearningTestrecognition(moreisbetter)
99.0(97.0-100.0)vs.96.0(92.0-98.0)(p0.013)
98.0vs.99.0(p0.176)
96.0vs.96.0(p0.575)
VerbalFluency(moreisbetter)
15.9(14.1-18.0)vs.15.3(13.7-16.8)(p0.594)
15.0vs.15.9(p0.233)
15.9vs.15.3(p0.152)
PhonologicalVerbalFluency(moreisbetter)
44.0(42.5-45.0)vs.25.9(21.6-36.1)(p0.021)
30.0vs.44.0(p0.028)
26.7vs.25.9(p0.271)
SemanticVerbalFluency(moreisbetter)
49.0(46.0-49.0)vs.38.0(33.5-43.5)(p0.123)
47.0vs.49.0(p0.373)
39vs.38.0(p0.396)
VisualSearchTest(moreisbetter)
49.0(45.6-50.0)vs.46.7(40.2-50.6)(p0.722)
46.2vs.49.0(p0.859)
46.7vs.46.7(p1.000)
TestofWeightsandMeasuresEstimation–Time(moreisbetter)
23.0(21.0-23.5)vs.22.0(18.0-25.0)(p0.512)
19.0vs.23.0(p0.038)
22.0vs.22.0(p0.776)
TestofWeightsandMeasuresEstimation–Weight(moreisbetter)
21.0(20.5-23.5)vs.20.0(15.5-21.5)(p0.08)
19.0vs.21.0(p0.027)
19vs.20.0(p0.843)
TestofWeightsandMeasuresEstimation–Total(moreisbetter)
45.0(41.5-46.0)vs.40.0(35.5-44.0)(p0.02)
38.0vs.45.0(p0.138)
40.0vs.40.0(p0.776)
Raven’sStandardProgressiveMatrices(moreisbetter)
30.0(28.5-33.5)vs.28.3(25.2-31.6)(p0.374)
25.7vs.30.0(p0.208)
28.3vs.28.3(p0.939)
Table 1. Changes in neurocognitive tests results after supplementation with probiotics (expressed asmedianvalues;interquartilerangeisreportedbetweenbrackets).
VerbalSpanforward(moreisbetter)
5.0(5.0-6.0)vs.5.2(4.6-6.0)(p0.551)
5.0vs.5.0(p0.121)
5.2vs.5.2(p0.632)
VerbalSpanbackward(moreisbetter)
5.0(4.0-5.0)vs.4.0(3.75-5.0)(p0.206)
5.0vs.5.0(p1.000)
4.0vs.4.0(p0.344)
CorsiBlockTappingTestforward(moreisbetter)
5.2(5.0-5.5)vs.5.2(5.0-6.0)(p0.888)
4.7vs.5.2(p0.049)
5.5vs.5.2(p0.980)
CorsiBlockTappingTestbackward(moreisbetter)
4.0(4.0-4.5)vs.5.0(4.0-5.0)(p0.102)
4.0vs.4.0(p0.180)
5.0vs.5.0(p0.317)
AachenerAphasiaTest(moreisbetter)
9.0(9.0-9.0)vs.9.0(9.0-9.0)(p1.000)
9.0vs.9.0(p1.000)
9.0vs.9.0(p1.000)
TrailMakingTestA(sec.)(lessisbetter)
43.0(39.0-53.0)vs.51.0(40.5-65.5)(p0.674)
50.0vs.43.0(p0.041)
50.0vs.51.0(p0.747)
TrailMakingTestB(sec.)(lessisbetter)
120.0(76.0-138.0)vs.98.0(78.5-146.0)(p0.138)
115.0vs.120.0
(p0.726)
97.0vs.98.0(p0.279)
Neurocognitivetests
Probioticssupplementationgroup
vs.Controlgroup(T6vs.T12)
Probioticssupplementationgroup(T0vs.T6)
Controlgroup
(T0vs.T12)
Rey-OsterriethComplexFigureimmediaterecall(moreisbetter)
22.0(19.0-23.7)vs.14.7(8.8-20.3)(p0.011)
16.6vs.22.0(p0.007)
13.1vs.14.7(p0.603)
Rey-OsterriethComplexFiguredelayedrecall(moreisbetter)
22.4(22.0-25.5)vs.12.6(5.7-19.1)(p0.011)
15.5vs.22.4(p0.008)
11.6vs.12.6(p0.369)
ReyAuditoryVerbalLearningTestimmediaterecall(moreisbetter)
53.0(49.3-55.6)vs.32.5(28.7-37.5)(p0.008)
46.0vs.53.0(p0.028)
30.6vs.32.5(p0.619)
ReyAuditoryVerbalLearningTestdelayedrecall(moreisbetter)
12.0(10.7-13.8)vs.5.3(4.3-8.0)(p0.008)
9.2vs.12.0(p0.034)
5.2vs.5.3(p0.241)
ReyAuditoryVerbalLearningTestrecognition(moreisbetter)
99.0(97.0-100.0)vs.96.0(92.0-98.0)(p0.013)
98.0vs.99.0(p0.176)
96.0vs.96.0(p0.575)
VerbalFluency(moreisbetter)
15.9(14.1-18.0)vs.15.3(13.7-16.8)(p0.594)
15.0vs.15.9(p0.233)
15.9vs.15.3(p0.152)
PhonologicalVerbalFluency(moreisbetter)
44.0(42.5-45.0)vs.25.9(21.6-36.1)(p0.021)
30.0vs.44.0(p0.028)
26.7vs.25.9(p0.271)
SemanticVerbalFluency(moreisbetter)
49.0(46.0-49.0)vs.38.0(33.5-43.5)(p0.123)
47.0vs.49.0(p0.373)
39vs.38.0(p0.396)
VisualSearchTest(moreisbetter)
49.0(45.6-50.0)vs.46.7(40.2-50.6)(p0.722)
46.2vs.49.0(p0.859)
46.7vs.46.7(p1.000)
TestofWeightsandMeasuresEstimation–Time(moreisbetter)
23.0(21.0-23.5)vs.22.0(18.0-25.0)(p0.512)
19.0vs.23.0(p0.038)
22.0vs.22.0(p0.776)
TestofWeightsandMeasuresEstimation–Weight(moreisbetter)
21.0(20.5-23.5)vs.20.0(15.5-21.5)(p0.08)
19.0vs.21.0(p0.027)
19vs.20.0(p0.843)
TestofWeightsandMeasuresEstimation–Total(moreisbetter)
45.0(41.5-46.0)vs.40.0(35.5-44.0)(p0.02)
38.0vs.45.0(p0.138)
40.0vs.40.0(p0.776)
Raven’sStandardProgressiveMatrices(moreisbetter)
30.0(28.5-33.5)vs.28.3(25.2-31.6)(p0.374)
25.7vs.30.0(p0.208)
28.3vs.28.3(p0.939)
Zilberman-Schapira, G.; Zmora, N.; Itav, S.; Bashiardes, S.; Elinav, H.; Elinav, E. The gut microbiome inhuman immunodeficiency virus infection.BMC Med.2016,14, 83; Tincati, C.; Douek, D.; Marchetti, G. Gut barrier structure, mucosal immunity and intestinal microbiota inthe pathogenesis and treatment of HIV infection.AIDS Res. Ther.2016,13, 19; D’ettorre, G.; Ceccarelli, G.; Giustini, N.; Serafino, S.; Calantone, N.; de Girolamo, G.; Bianchi, L.; Bellelli, V.;Ascoli-Bartoli, T.; Marcellini, S. Probiotics Reduce Inflammation in Antiretroviral Treated, HIV-InfectedIndividuals: Results of the “Probio-HIV” Clinical Trial.PLoS ONE2015,10, e0137200.