Amelioration of gut dysbiosis-induced cognitive deterioration by repeated administration of human clostridium butyricum: targeting intestinal and blood–brain barrier

Abstract Background Disturbed intestinal integrity and increased permeability are linked to dysbiosis. This disruption involves GIT-related and unrelated diseases, such as neurological diseases. Intake of a high-fat diet (HFD) leads to an imbalance of gut microbiota and regression of bacteria produc...

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Main Authors: Dalia Azmy Elberry, Maha Gamal, Zeinab Gawish, Esraa A. Hegazy, Sara Adel Hosny, Laila Ahmed Rashed, Marwa Nagi Mehesen, Asmaa Mohammed ShamsEldeen
Format: Article
Language:English
Published: SpringerOpen 2025-07-01
Series:Future Journal of Pharmaceutical Sciences
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Online Access:https://doi.org/10.1186/s43094-025-00836-0
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author Dalia Azmy Elberry
Maha Gamal
Zeinab Gawish
Esraa A. Hegazy
Sara Adel Hosny
Laila Ahmed Rashed
Marwa Nagi Mehesen
Asmaa Mohammed ShamsEldeen
author_facet Dalia Azmy Elberry
Maha Gamal
Zeinab Gawish
Esraa A. Hegazy
Sara Adel Hosny
Laila Ahmed Rashed
Marwa Nagi Mehesen
Asmaa Mohammed ShamsEldeen
author_sort Dalia Azmy Elberry
collection DOAJ
description Abstract Background Disturbed intestinal integrity and increased permeability are linked to dysbiosis. This disruption involves GIT-related and unrelated diseases, such as neurological diseases. Intake of a high-fat diet (HFD) leads to an imbalance of gut microbiota and regression of bacteria producing “short-chain fatty acids (SCFAs)”. These SCFAs can modulate brain functions. Therefore, we investigated the therapeutic effect of Clostridium Butyricum (CB) bacteria extracted from human faeces on intestinal and neurological impairments induced by HFD and explored their modulation of tight junction protein expression. Materials and methods Twenty-four adult male rats were classified into the control group, which received regular rat chow; the HFD group, which received HFD for 16 weeks; and the HFD-Microbiota group, which received HFD as in group II for 16 weeks, but from week 9 received CB (dose of 2 ml (2.3 × 1011 cfu/ml) daily till scarification. Results The microbiota improved working memory, episodic-like memory, and emotional memory. Also, there was a substantial decline in the animals’ body weights, serum lipopolysaccharides, interleukin-1β, tumour necrosis factor-α, insulin, glucose, and HOMA index compared to the HFD group. A remarkable increase in brain and colonic claudin-5 and occluding expression of its gene in the microbiota-treated group in comparison with the HFD group was reported. SCFAs, intestinal, brain claudin-5, and occludin genes were positively correlated. Also, a positive correlation was found between the F/B ratio and both brain beta-amyloid and Tau proteins. Conclusion Repeated intake of CB hindered systemic /neuroinflammation, enhanced the tight junction proteins’ expression in the gut/brain barrier, and improved cognitive functions.
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spelling doaj-art-9e5f907f9ae34d2ba942a0f0cbcd5c1b2025-08-20T04:01:53ZengSpringerOpenFuture Journal of Pharmaceutical Sciences2314-72532025-07-0111111810.1186/s43094-025-00836-0Amelioration of gut dysbiosis-induced cognitive deterioration by repeated administration of human clostridium butyricum: targeting intestinal and blood–brain barrierDalia Azmy Elberry0Maha Gamal1Zeinab Gawish2Esraa A. Hegazy3Sara Adel Hosny4Laila Ahmed Rashed5Marwa Nagi Mehesen6Asmaa Mohammed ShamsEldeen7Department of Medical Physiology, Faculty of Medicine, Cairo UniversityDepartment of Medical Physiology, Faculty of Medicine, Cairo UniversityDepartment of Medical Physiology, Faculty of Medicine, Cairo UniversityDepartment of Microbiology, Faculty of Medicine, Cairo UniversityDepartment of Histology and Cell Biology, Faculty of Medicine, Cairo UniversityDepartment of Biochemistry and Molecular Biology, Faculty of Medicine, Cairo UniversityDepartment of Medical Pharmacology, Faculty of Medicine, Cairo UniversityDepartment of Medical Physiology, Faculty of Medicine, Cairo UniversityAbstract Background Disturbed intestinal integrity and increased permeability are linked to dysbiosis. This disruption involves GIT-related and unrelated diseases, such as neurological diseases. Intake of a high-fat diet (HFD) leads to an imbalance of gut microbiota and regression of bacteria producing “short-chain fatty acids (SCFAs)”. These SCFAs can modulate brain functions. Therefore, we investigated the therapeutic effect of Clostridium Butyricum (CB) bacteria extracted from human faeces on intestinal and neurological impairments induced by HFD and explored their modulation of tight junction protein expression. Materials and methods Twenty-four adult male rats were classified into the control group, which received regular rat chow; the HFD group, which received HFD for 16 weeks; and the HFD-Microbiota group, which received HFD as in group II for 16 weeks, but from week 9 received CB (dose of 2 ml (2.3 × 1011 cfu/ml) daily till scarification. Results The microbiota improved working memory, episodic-like memory, and emotional memory. Also, there was a substantial decline in the animals’ body weights, serum lipopolysaccharides, interleukin-1β, tumour necrosis factor-α, insulin, glucose, and HOMA index compared to the HFD group. A remarkable increase in brain and colonic claudin-5 and occluding expression of its gene in the microbiota-treated group in comparison with the HFD group was reported. SCFAs, intestinal, brain claudin-5, and occludin genes were positively correlated. Also, a positive correlation was found between the F/B ratio and both brain beta-amyloid and Tau proteins. Conclusion Repeated intake of CB hindered systemic /neuroinflammation, enhanced the tight junction proteins’ expression in the gut/brain barrier, and improved cognitive functions.https://doi.org/10.1186/s43094-025-00836-0DysbiosisMicrobiotaHigh-fat dietShort-chain fatty acidClostridium butyricumTight junction protein
spellingShingle Dalia Azmy Elberry
Maha Gamal
Zeinab Gawish
Esraa A. Hegazy
Sara Adel Hosny
Laila Ahmed Rashed
Marwa Nagi Mehesen
Asmaa Mohammed ShamsEldeen
Amelioration of gut dysbiosis-induced cognitive deterioration by repeated administration of human clostridium butyricum: targeting intestinal and blood–brain barrier
Future Journal of Pharmaceutical Sciences
Dysbiosis
Microbiota
High-fat diet
Short-chain fatty acid
Clostridium butyricum
Tight junction protein
title Amelioration of gut dysbiosis-induced cognitive deterioration by repeated administration of human clostridium butyricum: targeting intestinal and blood–brain barrier
title_full Amelioration of gut dysbiosis-induced cognitive deterioration by repeated administration of human clostridium butyricum: targeting intestinal and blood–brain barrier
title_fullStr Amelioration of gut dysbiosis-induced cognitive deterioration by repeated administration of human clostridium butyricum: targeting intestinal and blood–brain barrier
title_full_unstemmed Amelioration of gut dysbiosis-induced cognitive deterioration by repeated administration of human clostridium butyricum: targeting intestinal and blood–brain barrier
title_short Amelioration of gut dysbiosis-induced cognitive deterioration by repeated administration of human clostridium butyricum: targeting intestinal and blood–brain barrier
title_sort amelioration of gut dysbiosis induced cognitive deterioration by repeated administration of human clostridium butyricum targeting intestinal and blood brain barrier
topic Dysbiosis
Microbiota
High-fat diet
Short-chain fatty acid
Clostridium butyricum
Tight junction protein
url https://doi.org/10.1186/s43094-025-00836-0
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