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Gut microbiota alterations in autism spectrum disorder: Implications for microbiota‑gut‑brain axis mechanisms and therapeutic strategies (Review)

  • Authors:
    • Sarah S. Alkhaldi
    • Mohamed O. Mohamed
    • Rahiq A. Alyahya
    • Omar Mahmood Al‑Azzawi
    • Heba M. Karmy
    • Amany M. Shehata
    • Rasha Alnefaie
    • Ola A. Attia
    • Nada Abdelmonaem
    • Reda M. Mansour
    • Mohamed M. Waly
  • View Affiliations / Copyright

    Affiliations: Department of Psychiatry, Faculty of Medicine, Arabian Gulf University, Manama 31952, Kingdom of Bahrain, Agriculture Biotechnology Program, Faculty of Agriculture, Ain Shams University, Cairo 11241, Egypt, Faculty of Pharmacy, İstinye University, Istanbul 34396, Türkiye, Biotechnology Department, Animal Health Research Institute (AHRI), Agriculture Research Center (ARC), Giza 12618, Egypt, Department of Chemistry and Microbiology, Faculty of Science, Menoufia University, Shebin El‑Kom, Menofia Governorate 614465, Egypt, Department of Biology, Faculty of Science, Al‑Baha University, Albaha 65779, Kingdom of Saudi Arabia, Department of Biotechnology and Genetic Engineering, Faculty of Agriculture, Benha University, Benha 13518, Egypt, Department of Chemistry and Biochemistry, Faculty of Science, Zagazig University, Zagazig 44511, Egypt, Department of Zoology and Entomology, Faculty of Science, Helwan University, Cairo 11795, Egypt, The Biotechnology and Genetic Engineering Program, Faculty of Science, Helwan National University, Helwan Sharkeya, Cairo Governate 4037120, Egypt
    Copyright: © Alkhaldi et al. This is an open access article distributed under the terms of Creative Commons Attribution License [CC BY 4.0].
  • Article Number: 49
    |
    Published online on: April 17, 2026
       https://doi.org/10.3892/wasj.2026.464
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Abstract

Autism spectrum disorder (ASD) is a complex neurodevelopmental condition often accompanied by chronic gastrointestinal (GI) disturbances. Recent evidence suggests that these GI issues may be biologically linked to ASD through the microbiota‑gut‑brain axis (MGBA). The present review aimed to highlight how alterations in the gut microbiota contribute to ASD symptoms and to explore potential microbiome‑based therapeutic strategies. Recent research findings regarding gut microbial composition in individuals with ASD were reviewed, focusing on changes in beneficial and harmful microbial taxa, associated inflammatory and metabolic alterations, and their implications for neural signaling within the MGBA. Data on emerging therapeutic interventions, such as probiotics, prebiotics, and fecal microbiota transplantation, were also evaluated. Studies reveal notable microbial dysbiosis in ASD, including reduced levels of Bifidobacterium and Prevotella and an increased abundance of Clostridium species. These alterations are linked to intestinal inflammation, impaired gut barrier integrity, and disturbances in neurotransmitter production. Furthermore, the highly restricted dietary patterns and food selectivity commonly observed in individuals with ASD are likely to reduce microbial diversity, particularly affecting fiber‑dependent taxa, such as Prevotella. Concurrently, the severity of specific ASD traits, particularly repetitive and rigid behaviors, has been closely correlated with GI discomfort and distinct microbial imbalances. Microbial metabolites, such as short‑chain fatty acids, appear to influence brain function, mood, and social behavior. Initial therapeutic trials indicate that microbiota‑targeted interventions may improve both GI symptoms and behavioral outcomes. Current evidence supports a significant association between alterations in the gut microbiota and ASD pathophysiology via the bidirectional MGBA. While further studies are required to establish causality and refine therapeutic approaches, emerging microbiota‑based treatments highlight the importance of adopting a holistic model that integrates neurological, immunological, and microbial aspects in understanding and managing ASD. However, the strength of mechanistic evidence varies across immune, neural, and endocrine pathways, with immune‑related mechanisms supported by the most consistent ASD‑specific data.
View Figures

Figure 1

Schematic overview of the
bidirectional communication between the central nervous system and
the gastrointestinal tract via the microbiota-gut-brain axis
(MGBA). Commensal gut microorganisms interact with intestinal
epithelial cells, immune cells and the enteric nervous system.
Signals are transmitted through neural pathways, particularly the
vagus nerve, as well as immune and metabolic routes, enabling
reciprocal gut-brain communication. Enteric nerve fibers are
depicted within the intestinal wall (lamina propria and submucosal
layers) and do not extend into the intestinal lumen. Neural
activation is illustrated as an indirect process mediated through
epithelial signaling, immune cell activation, and microbial
metabolites rather than direct bacterial-neuronal contact.

Figure 2

Mechanistic illustration of proposed
pathways through which gut dysbiosis may influence neurobiological
processes relevant to ASD. Alterations in gut microbial composition
may contribute to increased intestinal permeability, immune
activation, and changes in microbial metabolites such as SCFAs and
LPS. These signals may reach the brain through systemic circulation
or neural pathways, including the vagus nerve, potentially
contributing to neuroimmune modulation and altered
neurotransmission. The pathways shown are hypothesis-generating and
are not indicative of established causality. ASD, autism spectrum
disorder; SCFAs, short-chain fatty acids; LPS,
lipopolysaccharides.

Figure 3

Conceptual comparison of gut
microbiota composition in neurotypical individuals and individuals
with ASD, as reported in some cohorts. Neurotypical gut microbiota
is generally characterized by higher microbial diversity and
increased abundance of beneficial taxa such as
Bifidobacterium and Prevotella. By contrast,
ASD-associated dysbiosis has been described in some studies by
reduced microbial diversity and increased abundance of specific
taxa, including Clostridium species. These patterns are
variable and not consistently observed across all populations. ASD,
autism spectrum disorder.

Figure 4

Conceptual diagram illustrating key
factors proposed to influence gut microbiota composition in
individuals with ASD. These factors include dietary patterns,
antibiotic exposure, mode of delivery (vaginal vs. cesarean), host
genetic background, and environmental influences such as stress and
lifestyle. The combined effects of these factors may contribute to
inter-individual variability in gut microbiota profiles observed
across ASD populations. ASD, autism spectrum disorder.

Figure 5

Conceptual overview of the
microbiota-gut-brain axis in autism spectrum disorders. Gut
dysbiosis is hypothesized to influence neurodevelopment through
microbial metabolites, neuroendocrine signaling, immune modulation,
and neural pathways. Therapeutic approaches targeting the gut
microbiota are shown illustratively to indicate potential points of
intervention within this axis, without implying established
clinical efficacy.

Figure 6

Overview of gut microbiota-targeted
interventions explored in ASD. Approaches such as probiotics,
prebiotics, synbiotics, fecal microbiota transplantation and
dietary modification are hypothesized to modulate gut microbial
composition and microbiota-gut-brain signaling. These interventions
may influence gastrointestinal symptoms, gut barrier integrity and
neuroimmune pathways, although reported effects on core ASD
symptoms remain variable across studies. ASD, autism spectrum
disorder.

Figure 7

Evidence hierarchy summarizing the
current landscape of gut microbiome intervention studies in ASD.
The pyramid illustrates increasing levels of evidence from in
vitro studies and animal models to open-label clinical trials
and randomized controlled trials. While higher levels of evidence
provide greater rigor and generalizability, they are also
associated with methodological challenges, including heterogeneity,
limited sample sizes, and variability in intervention protocols.
ASD, autism spectrum disorder.
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Copy and paste a formatted citation
Spandidos Publications style
Alkhaldi SS, Mohamed MO, Alyahya RA, Al‑Azzawi OM, Karmy HM, Shehata AM, Alnefaie R, Attia OA, Abdelmonaem N, Mansour RM, Mansour RM, et al: Gut microbiota alterations in autism spectrum disorder: Implications for microbiota‑gut‑brain axis mechanisms and therapeutic strategies (Review). World Acad Sci J 8: 49, 2026.
APA
Alkhaldi, S.S., Mohamed, M.O., Alyahya, R.A., Al‑Azzawi, O.M., Karmy, H.M., Shehata, A.M. ... Waly, M.M. (2026). Gut microbiota alterations in autism spectrum disorder: Implications for microbiota‑gut‑brain axis mechanisms and therapeutic strategies (Review). World Academy of Sciences Journal, 8, 49. https://doi.org/10.3892/wasj.2026.464
MLA
Alkhaldi, S. S., Mohamed, M. O., Alyahya, R. A., Al‑Azzawi, O. M., Karmy, H. M., Shehata, A. M., Alnefaie, R., Attia, O. A., Abdelmonaem, N., Mansour, R. M., Waly, M. M."Gut microbiota alterations in autism spectrum disorder: Implications for microbiota‑gut‑brain axis mechanisms and therapeutic strategies (Review)". World Academy of Sciences Journal 8.3 (2026): 49.
Chicago
Alkhaldi, S. S., Mohamed, M. O., Alyahya, R. A., Al‑Azzawi, O. M., Karmy, H. M., Shehata, A. M., Alnefaie, R., Attia, O. A., Abdelmonaem, N., Mansour, R. M., Waly, M. M."Gut microbiota alterations in autism spectrum disorder: Implications for microbiota‑gut‑brain axis mechanisms and therapeutic strategies (Review)". World Academy of Sciences Journal 8, no. 3 (2026): 49. https://doi.org/10.3892/wasj.2026.464
Copy and paste a formatted citation
x
Spandidos Publications style
Alkhaldi SS, Mohamed MO, Alyahya RA, Al‑Azzawi OM, Karmy HM, Shehata AM, Alnefaie R, Attia OA, Abdelmonaem N, Mansour RM, Mansour RM, et al: Gut microbiota alterations in autism spectrum disorder: Implications for microbiota‑gut‑brain axis mechanisms and therapeutic strategies (Review). World Acad Sci J 8: 49, 2026.
APA
Alkhaldi, S.S., Mohamed, M.O., Alyahya, R.A., Al‑Azzawi, O.M., Karmy, H.M., Shehata, A.M. ... Waly, M.M. (2026). Gut microbiota alterations in autism spectrum disorder: Implications for microbiota‑gut‑brain axis mechanisms and therapeutic strategies (Review). World Academy of Sciences Journal, 8, 49. https://doi.org/10.3892/wasj.2026.464
MLA
Alkhaldi, S. S., Mohamed, M. O., Alyahya, R. A., Al‑Azzawi, O. M., Karmy, H. M., Shehata, A. M., Alnefaie, R., Attia, O. A., Abdelmonaem, N., Mansour, R. M., Waly, M. M."Gut microbiota alterations in autism spectrum disorder: Implications for microbiota‑gut‑brain axis mechanisms and therapeutic strategies (Review)". World Academy of Sciences Journal 8.3 (2026): 49.
Chicago
Alkhaldi, S. S., Mohamed, M. O., Alyahya, R. A., Al‑Azzawi, O. M., Karmy, H. M., Shehata, A. M., Alnefaie, R., Attia, O. A., Abdelmonaem, N., Mansour, R. M., Waly, M. M."Gut microbiota alterations in autism spectrum disorder: Implications for microbiota‑gut‑brain axis mechanisms and therapeutic strategies (Review)". World Academy of Sciences Journal 8, no. 3 (2026): 49. https://doi.org/10.3892/wasj.2026.464
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