beneficial effect of 6 months of probiotics on ... · gabriella di girolamo1, giancarlo...

1
Abstract n. 419 BENEFICIAL EFFECT OF 6 MONTHS OF PROBIOTICS ON ASYMPTOMATIC NEUROCOGNITIVE IMPAIRMENT Luigi Celani 1 , Eugenio N Cavallari 1 , Mariangela Fratino 1 , Claudia Pinacchio 1 , Giuseppe Corano-Scheri 1 , Gabriella Di Girolamo 1 , Giancarlo Ceccarelli 1 , Claudio M. Mastroianni 1 , Carolina Scagnolari 1 , Vincenzo Vullo 1 , Gabriella d'Ettorre 1 . 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 Celani Department of Public Health and Infectious Diseases “Sapienza” University of Rome [email protected] BACKGROUND HIV infected subjects show high prevalence of mild neurocognitive symptoms; individuals with Asymptomatic Neurocognitive Impairment (ANI) show increased risk of future symptomatic decline but to date 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’s microbiome can affect the modulation of the gut-brain axis, thus resulting in the onset of behavioral and neurocognitive alterations. For these reasons, the use of probiotics represents a novel potential approach to manage conditions, and to ameliorate cognitive function in several pathological settings. METHODS 35 HIV infected individuals successfully treated with HAART were enrolled in this unblinded, non- randomized study. At baseline (T0) a battery of 20 neurocognitive tests was administered to evaluate patients’ cognitive function and a lumbar puncture was performed to determine neopterin concentration in cerebrospinal fluid (CSF). Subsequently, 9 participants underwent a 6 months course of antiretroviral therapy supplementation with a commercially available oral probiotic (2 sachets, each containing 450x10 9 billion bacteria, twice a day, available in USA as Visbiome® in Europe as Vivomixx® conteinig: Lactobacillus plantarum, Streptococcus thermophilus, 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 a second neurocognitive tests assay, whereas controls underwent a second battery of neurocognitive tests after 12 months (T12). RESULTS At T0 demographics, variables related to infection and neurocognitive tests results were similar between the two groups; all participants showed an abnormal result in at least one test exploring the executive functions 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 was correlated 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 modifications were observed between T0 and T12 in controls. CONCLUSIONS Supplementation with this specific probiotic could represent a useful strategy to ameliorate cognitive function in HIV infected individuals with ANI. Further investigations are needed to define the long term benefits of supplementation with this product. Neurocognitive tests Probiotics supplementation group vs. Control group (T6 vs.T12) Probiotics supplement ation group (T0 vs. T6) Control group (T0 vs. T12) Rey-Osterrieth Complex Figure immediate recall (more is better) 22.0 (19.0-23.7) vs. 14.7 (8.8-20.3) (p 0.011) 16.6 vs. 22.0 (p 0.007) 13.1 vs. 14.7 (p 0.603) Rey-Osterrieth Complex Figure delayed recall (more is better) 22.4 (22.0-25.5) vs. 12.6 (5.7-19.1) (p 0.011) 15.5 vs. 22.4 (p 0.008) 11.6 vs. 12.6 (p 0.369) Rey Auditory Verbal Learning Test immediate recall (more is better) 53.0 (49.3-55.6) vs. 32.5 (28.7-37.5) (p 0.008) 46.0 vs. 53.0 (p 0.028) 30.6 vs. 32.5 (p 0.619) Rey Auditory Verbal Learning Test delayed recall (more is better) 12 .0 (10.7-13.8) vs. 5.3 (4.3-8.0) (p 0.008) 9.2 vs. 12.0 (p 0.034) 5.2 vs. 5.3 (p 0.241) Rey Auditory Verbal Learning Test recognition (more is better) 99.0 (97.0-100.0) vs. 96.0 (92.0-98.0) (p 0.013) 98.0 vs. 99.0 (p 0.176) 96.0 vs. 96.0 (p 0.575) Verbal Fluency (more is better) 15.9 (14.1-18.0) vs. 15.3 (13.7-16.8) (p 0.594) 15.0 vs. 15.9 (p 0.233) 15.9 vs. 15.3 (p 0.152) Phonological Verbal Fluency (more is better) 44.0 (42.5-45.0) vs. 25.9 (21.6-36.1) (p 0.021) 30.0 vs. 44.0 (p 0.028) 26.7 vs. 25.9 (p 0.271) Semantic Verbal Fluency (more is better) 49.0 (46.0-49.0) vs. 38.0 (33.5-43.5) (p 0.123) 47.0 vs. 49.0 (p 0.373) 39 vs. 38.0 (p 0.396) Visual Search Test (more is better) 49.0 (45.6-50.0) vs. 46.7 (40.2-50.6) (p 0.722) 46.2 vs. 49.0 (p 0.859) 46.7 vs. 46.7 (p 1.000) Table 1. Changes in neurocognitive tests results after supplementation with probiotics (expressed as Verbal Span forward (more is better) 5.0 (5.0-6.0) vs. 5.2 (4.6-6.0) (p 0.551) 5.0 vs. 5.0 (p 0.121) 5.2 vs. 5.2 (p 0.632) Verbal Span backward (more is better) 5.0 (4.0-5.0) vs. 4.0 (3.75-5.0) (p 0.206) 5.0 vs. 5.0 (p 1.000) 4.0 vs. 4.0 (p 0.344) Corsi Block Tapping Test forward (more is better) 5.2 (5.0-5.5) vs. 5.2 (5.0-6.0) (p 0.888) 4.7 vs. 5.2 (p 0.049) 5.5 vs. 5.2 (p 0.980) Corsi Block Tapping Test backward (more is better) 4.0 (4.0-4.5) vs. 5.0 (4.0-5.0) (p 0.102) 4.0 vs. 4.0 (p 0.180) 5.0 vs. 5.0 (p 0.317) Aachener Aphasia Test (more is better) 9.0 (9.0-9.0) vs. 9.0 (9.0-9.0) (p 1.000) 9.0 vs. 9.0 (p 1.000) 9.0 vs. 9.0 (p 1.000) Trail Making Test A (sec.) (less is better) 43.0 (39.0-53.0) vs. 51.0 (40.5-65.5) (p 0.674) 50.0 vs. 43.0 (p 0.041) 50.0 vs. 51.0 (p 0.747) Trail Making Test B (sec.) (less is better) 120.0 (76.0-138.0) vs. 98.0 (78.5-146.0) (p 0.138) 115.0 vs. 120.0 (p 0.726) 97.0 vs. 98.0 (p 0.279) Test of Weights and Measures Estimation – Time (more is better) 23.0 (21.0-23.5) vs. 22.0 (18.0-25.0) (p 0.512) 19.0 vs. 23.0 (p 0.038) 22.0 vs. 22.0 (p 0.776) Test of Weights and Measures Estimation – Weight (more is better) 21.0 (20.5-23.5) vs. 20.0 (15.5-21.5) (p 0.08) 19.0 vs. 21.0 (p 0.027) 19 vs. 20.0 (p 0.843) Test of Weights and Measures Estimation – Total (more is better) 45.0 (41.5-46.0) vs. 40.0 (35.5-44.0) (p 0.02) 38.0 vs. 45.0 (p 0.138) 40.0 vs. 40.0 (p 0.776) Raven’s Standard Progressive Matrices (more is better) 30.0 (28.5-33.5) vs. 28.3 (25.2-31.6) (p 0.374) 25.7 vs. 30.0 (p 0.208) 28.3 vs. 28.3 (p 0.939) 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.

Upload: nguyenliem

Post on 03-Dec-2018

213 views

Category:

Documents


0 download

TRANSCRIPT

Page 1: BENEFICIAL EFFECT OF 6 MONTHS OF PROBIOTICS ON ... · Gabriella Di Girolamo1, Giancarlo Ceccarelli1, Claudio M. Mastroianni1, Carolina Scagnolari1, Vincenzo Vullo 1 , Gabriella d'Ettorre

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

[email protected]

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.