Normal gut microbiota modulates brain development and behavior

Heijtz, Rochellys Diaz; Wang, Shugui; Anuar, Farhana; Yu, Qian; Björkholm, Britta; Samuelsson, Annika; Hibberd, Martin L.; Forssberg, Hans; Pettersson, Sven

doi:10.1073/pnas.1010529108

Cited by 2,611 publications

(2,282 citation statements)

References 42 publications

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“…The hypothalamus and the brain stem are central sites of appetite regulation 11. The gut microbiome can stimulate vagal sensory neurons, which is a major neural pathway that conveys information from the gastrointestinal luminal contents to the brain and modulates gastrointestinal motility and feeding behavior 12, 13. The gut microbiome can influence neuronal signaling to the brain through vagal afferent neurons 14.…”

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confidence: 99%

Association of Obesity with Serum Leptin, Adiponectin, and Serotonin and Gut Microflora in Beagle Dogs

Park

Lee

Kim

et al. 2014

Veterinary Internal Medicne

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BackgroundSerotonin (5‐hydroxytryptamine, 5HT) is involved in hypothalamic regulation of energy consumption. Also, the gut microbiome can influence neuronal signaling to the brain through vagal afferent neurons. Therefore, serotonin concentrations in the central nervous system and the composition of the microbiota can be related to obesity.ObjectiveTo examine adipokine, and, serotonin concentrations, and the gut microbiota in lean dogs and dogs with experimentally induced obesity.AnimalsFourteen healthy Beagle dogs were used in this study.MethodsSeven Beagle dogs in the obese group were fed commercial food ad libitum, over a period of 6 months to increase their weight and seven Beagle dogs in lean group were fed a restricted amount of the same diet to maintain optimal body condition over a period of 6 months. Peripheral leptin, adiponectin, 5HT, and cerebrospinal fluid (CSF‐5HT) levels were measured by ELISA. Fecal samples were collected in lean and obese groups 6 months after obesity was induced. Targeted pyrosequencing of the 16S rRNA gene was performed using a Genome Sequencer FLX plus system.ResultsLeptin concentrations were higher in the obese group (1.98 ± 1.00) compared to those of the lean group (1.12 ± 0.07, P = .025). Adiponectin and 5‐hydroytryptamine of cerebrospinal fluid (CSF‐5HT) concentrations were higher in the lean group (27.1 ± 7.28) than in the obese group (14.4 ± 5.40, P = .018). Analysis of the microbiome revealed that the diversity of the microbial community was lower in the obese group. Microbes from the phylum Firmicutes (85%) were predominant group in the gut microbiota of lean dogs. However, bacteria from the phylum Proteobacteria (76%) were the predominant group in the gut microbiota of dogs in the obese group.Conclusions and Clinical ImportanceDecreased 5HT levels in obese group might increase the risk of obesity because of increased appetite. Microflora enriched with gram‐negative might be related with chronic inflammation status in obese dogs.

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confidence: 99%

Association of Obesity with Serum Leptin, Adiponectin, and Serotonin and Gut Microflora in Beagle Dogs

Park

Lee

Kim

et al. 2014

Veterinary Internal Medicne

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“…Recently, the studies illustrated the relevance of a striatum, which proved their hypothesis that the "healthy" gut microbiota is an integral part of the external environmental signals that modulate brain development and function (Heijtz et al, 2011). However, once the gut microbiota community is interrupted by multiple factors including maternal vertical transmission, genetic makeup of the individual, diet, medications such as antibiotics, GI infections and stress, the gut homeostasis is subsequently imbalanced and causes detrimental effects on CNS through gut-brain axis (Heijtz et al, 2011), while some other experiments concluded that the gut microbiota infl uence brain chemistry and behavior independently of the autonomic nervous system, GI-specifi c neurotransmitters, or infl ammation .…”

Section: The Gut-brain-liver Axismentioning

confidence: 99%

“…GF mice displayed increased motor activity and reduced anxiety, compared with SPF mice with normal gut microbiota (Heijtz et al, 2011). However, there needs to be additional studies required in analyzing the direct role of the gut microbiota influencing the gut-brain axis.…”

Section: Review Protein Cellmentioning

confidence: 99%

“…Animal-based research has extended the idea of microbiota-brain interactions to many psychiatric disorders and brain development. Studies indicate that behavioral changes induced by destabilization of the microbiota are likely to be mediated by substances of microbial origin acting on the host brain either directly or indirectly through neuro-active substances (Heijtz et al, 2011). However, it is still under debate, whether the gut microbiota metabolites are contributing towards the neural behavior or not.…”

Section: Review Protein Cellmentioning

confidence: 99%

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The role of gut microbiota in the gut-brain axis: current challenges and perspectives

2013

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Brain and the gastrointestinal (GI) tract are intimately connected to form a bidirectional neurohumoral communication system. The communication between gut and brain, knows as the gut-brain axis, is so well established that the functional status of gut is always related to the condition of brain. The researches on the gut-brain axis were traditionally focused on the psychological status affecting the function of the GI tract. However, recent evidences showed that gut microbiota communicates with the brain via the gut-brain axis to modulate brain development and behavioral phenotypes. These recent fi ndings on the new role of gut microbiota in the gut-brain axis implicate that gut microbiota could associate with brain functions as well as neurological diseases via the gut-brain axis. To elucidate the role of gut microbiota in the gut-brain axis, precise identification of the composition of microbes constituting gut microbiota is an essential step. However, identifi cation of microbes constituting gut microbiota has been the main technological challenge currently due to massive amount of intestinal microbes and the diffi culties in culture of gut microbes. Current methods for identifi cation of microbes constituting gut microbiota are dependent on omics analysis methods by using advanced high tech equipment. Here, we review the association of gut microbiota with the gut-brain axis, including the pros and cons of the current high throughput methods for identifi cation of microbes constituting gut microbiota to elucidate the role of gut microbiota in the gut-brain axis.

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“…L'impact du microbiote intestinal n'est pas limité à l'intestin, il s'exerce également à l'échelle systémique des organismes hôtes. Il régule en effet la maturation du système immunitaire [5,6], la croissance post-natale [7,8], et peut même influencer l'activité cérébrale [9,10,48] (➜). Chez l'homme, des perturbations du microbiote intestinal sont associées à une grande variété de pathologies d'ordre métabolique, immunitaire ou même cognitif [11,12].…”

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