New psychoactive probiotics? A gut bacteria may alleviate neuroinflammation via SCFAs


Roseburia hominis attenuates neuroinflammation using short-chain fatty acids by inhibiting histone deacetylases


On July 12, 2022, Duan Liping’s research group from Peking University and Liu Shuangjiang’s research group from the Institute of Microbiology, Chinese Academy of Sciences published in the international journal Molecular Nutrition & Food Research (Q1, IF: 6.57)

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Published research paper titled “Roseburia hominisAlleviates Neuroinflammation via Short-Chain Fatty Acids through Histone Deacetylase Inhibition”. On September 21, 2022, this article was selected as the cover article, and the cover image design was inspired by the ancient Chinese philosophy of “yin and yang”.

Neuroinflammation generally refers to an inflammatory response in the central nervous system (CNS), which can be caused by a variety of pathological stimuli, including infection, trauma, ischemia, and toxins. This process is always accompanied by the release of a series of cytokines such as IL-1β, IL-6, IL-18 and TNF-α, as well as chemokines such as MCP-1 and CCL5. In pathological conditions, activated microglia produce more inflammatory factors, which may help clear pathogens or toxins, but also lead to neuronal dysfunction and damage. Neuroinflammation plays an important role in the pathogenesis of Alzheimer’s disease, Parkinson’s disease and major depressive disorder. Inhibiting neuroinflammation can significantly improve the damage of the central nervous system and prevent the onset of related neurological diseases. Therefore, inhibiting neuroinflammation is one of the most promising approaches to treat these neurodegenerative diseases or brain injuries.

The gut microbiota communicates closely with the central nervous system to regulate brain function and behavior. Recent studies have reported that the gut microbiota influences neuroinflammation through the gut-brain axis. In a previous study by this group, oral administration of R. hominis, an obligate Gram-positive anaerobic bacterium, significantly ameliorated visceral hypersensitivity in a rat model induced by chronic water-avoidance stress response and decreased corticotropin-releasing hormone levels in serum, but whether R. hominis might affect neuroinflammation, the underlying mechanism remains unclear. R. hominis is characterized by the production of short-chain fatty acids (SCFA). SCFAs can cross the blood-brain barrier and modulate the immune function of microglia. However, whether R. hominis can improve neuroinflammation by promoting SCFA production remains unclear.

Germ-free (GF) animals exhibit abnormal behavior and physiology. In this study, GF rats were used to assess the effect of R. hominis on neuroinflammation by detecting microglial activation. This paper also assessed the effect of R. hominis on serum SCFA levels and histone deacetylase 1 (HDAC1) expression. This study provides a new approach to alleviate neuroinflammation by supplementing the candidate psychoactive probiotic R. hominis.

Study overview

Gut microbiota plays an important role in gut-brain interactions, and gut microbiota dysbiosis is associated with neuroinflammation. However, specific probiotics targeting neuroinflammation need to be explored. In this study, the anti-neuroinflammatory effects and underlying mechanisms of the candidate probiotic, R. hominis, were investigated.

First, germ-free (GF) rats were orally treated with R. hominis. Microglial activation, pro-inflammatory cytokines, short-chain fatty acid levels, depressive behavior, and visceral sensitivity were then assessed.

Second, GF rats were treated with propionate or butyrate to analyze microglial activation, pro-inflammatory cytokines, histone deacetylase 1 (HDAC1) and histone H3 Acetyl K9 (Ac-H3K9).

The results showed that feeding R. hominis inhibited microglia activation, decreased the levels of IL-1α, INF-γ and MCP-1 in the brain, and alleviated depression in GF rats Behavioral and visceral hypersensitivity responses. In addition, serum levels of propionate and butyrate were significantly increased in the R. hominis-treated group. Propionate or butyrate treatment decreased microglial activation, levels of pro-inflammatory cytokines and HDAC1, and promoted Ac-H3K9 expression in the brain.

These findings suggest that R. hominis reduces neuroinflammation by producing propionate and butyrate, which act as HDAC inhibitors. This study provides a candidate psychoactive probiotic to reduce neuroinflammation.

Picture and text appreciation

Figure 1. R. hominis reduces microglial activation in germ-free rats.

Figure 2. Effects of R. hominis on proinflammatory cytokine and chemokine levels in rat brain.

Figure 3. Serum concentrations of short-chain fatty acids in rats.

Figure 4. Propionate or butyrate reduces microglial activation in germ-free (GF) rats.

Figure 5. Propionate and butyrate significantly reduced levels of proinflammatory cytokines and chemokines in rat brain.

Figure 6. Propionate and butyrate inhibit HDAC1 expression and increase Ac-H3K9 levels in GF rat microglia.

Figure 7. R. hominis inhibits HDAC1 expression and increases Ac-H3K9 levels in GF rat microglia.