Gut instincts: microbiota as a key regulator of brain development, ageing and neurodegeneration.

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Abstract

There is a growing realisation that the gut-brain axis and its regulation by the microbiota may play a key role in the biological and physiological basis of neurodevelopmental, age-related and neurodegenerative disorders. The routes of communication between the microbiota and brain are being unravelled and include the vagus nerve, gut hormone signalling, the immune system, tryptophan metabolism or by way of microbial metabolites such as short chain fatty acids. The importance of early life gut microbiota in shaping future health outcomes is also emerging. Disturbances of this composition by way of antibiotic exposure, lack of breastfeeding, infection, stress and the environmental influences coupled with the influence of host genetics can result in long-term effects on physiology and behaviour, at least in animal models. It is also worth noting that mode of delivery at birth influences microbiota composition with those born by Caesarean section having a distinctly different microbiota in early life to those born per vaginum. At the other extreme of life, ageing is associated with a narrowing in microbial diversity and healthy ageing correlates with a diverse microbiome. Recently, the gut microbiota has been implicated in a variety of conditions including depression, autism, schizophrenia and Parkinson's disease. There is still considerable debate as to whether or not the gut microbiota changes are core to the pathophysiology of such conditions or are merely epiphenomenal. It is plausible that such neuropsychiatric disorders might be treated in the future by targeting the microbiota either by microbiota transplantation, antibiotics or psychobiotics.

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Through Ageing, and Beyond: Gut Microbiota and Inflammatory Status in Seniors and Centenarians

Elena Biagi, Lotta Nylund, Marco Candela … (2010)

Background Age-related physiological changes in the gastrointestinal tract, as well as modifications in lifestyle, nutritional behaviour, and functionality of the host immune system, inevitably affect the gut microbiota, resulting in a greater susceptibility to infections. Methodology/Principal Findings By using the Human Intestinal Tract Chip (HITChip) and quantitative PCR of 16S rRNA genes of Bacteria and Archaea, we explored the age-related differences in the gut microbiota composition among young adults, elderly, and centenarians, i.e subjects who reached the extreme limits of the human lifespan, living for over 100 years. We observed that the microbial composition and diversity of the gut ecosystem of young adults and seventy-years old people is highly similar but differs significantly from that of the centenarians. After 100 years of symbiotic association with the human host, the microbiota is characterized by a rearrangement in the Firmicutes population and an enrichment in facultative anaerobes, notably pathobionts. The presence of such a compromised microbiota in the centenarians is associated with an increased inflammatory status, also known as inflammageing, as determined by a range of peripheral blood inflammatory markers. This may be explained by a remodelling of the centenarians' microbiota, with a marked decrease in Faecalibacterium prauznitzii and relatives, symbiotic species with reported anti-inflammatory properties. As signature bacteria of the long life we identified specifically Eubacterium limosum and relatives that were more than ten-fold increased in the centenarians. Conclusions/Significance We provide evidence for the fact that the ageing process deeply affects the structure of the human gut microbiota, as well as its homeostasis with the host's immune system. Because of its crucial role in the host physiology and health status, age-related differences in the gut microbiota composition may be related to the progression of diseases and frailty in the elderly population.

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Long-term potentiation and memory.

M A Lynch (2004)

One of the most significant challenges in neuroscience is to identify the cellular and molecular processes that underlie learning and memory formation. The past decade has seen remarkable progress in understanding changes that accompany certain forms of acquisition and recall, particularly those forms which require activation of afferent pathways in the hippocampus. This progress can be attributed to a number of factors including well-characterized animal models, well-defined probes for analysis of cell signaling events and changes in gene transcription, and technology which has allowed gene knockout and overexpression in cells and animals. Of the several animal models used in identifying the changes which accompany plasticity in synaptic connections, long-term potentiation (LTP) has received most attention, and although it is not yet clear whether the changes that underlie maintenance of LTP also underlie memory consolidation, significant advances have been made in understanding cell signaling events that contribute to this form of synaptic plasticity. In this review, emphasis is focused on analysis of changes that occur after learning, especially spatial learning, and LTP and the value of assessing these changes in parallel is discussed. The effect of different stressors on spatial learning/memory and LTP is emphasized, and the review concludes with a brief analysis of the contribution of studies, in which transgenic animals were used, to the literature on memory/learning and LTP.

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Gut Microbiota and Extreme Longevity.

Elena Biagi, Claudio Franceschi, Simone Rampelli … (2016)

The study of the extreme limits of human lifespan may allow a better understanding of how human beings can escape, delay, or survive the most frequent age-related causes of morbidity, a peculiarity shown by long-living individuals. Longevity is a complex trait in which genetics, environment, and stochasticity concur to determine the chance to reach 100 or more years of age [1]. Because of its impact on human metabolism and immunology, the gut microbiome has been proposed as a possible determinant of healthy aging [2, 3]. Indeed, the preservation of host-microbes homeostasis can counteract inflammaging [4], intestinal permeability [5], and decline in bone and cognitive health [6, 7]. Aiming at deepening our knowledge on the relationship between the gut microbiota and a long-living host, we provide for the first time the phylogenetic microbiota analysis of semi-supercentenarians, i.e., 105-109 years old, in comparison to adults, elderly, and centenarians, thus reconstructing the longest available human microbiota trajectory along aging. We highlighted the presence of a core microbiota of highly occurring, symbiotic bacterial taxa (mostly belonging to the dominant Ruminococcaceae, Lachnospiraceae, and Bacteroidaceae families), with a cumulative abundance decreasing along with age. Aging is characterized by an increasing abundance of subdominant species, as well as a rearrangement in their co-occurrence network. These features are maintained in longevity and extreme longevity, but peculiarities emerged, especially in semi-supercentenarians, describing changes that, even accommodating opportunistic and allochthonous bacteria, might possibly support health maintenance during aging, such as an enrichment and/or higher prevalence of health-associated groups (e.g., Akkermansia, Bifidobacterium, and Christensenellaceae).