Mid-life microbiota crises: middle age is associated with pervasive neuroimmune alterations that are reversed by targeting the gut microbiome

Boehme, Marcus; Wouw, Marcel van de; Bastiaanssen, Thomaz F.S.; Olavarría-Ramírez, Loreto; Lyons, Katríona; Fouhy, Fiona; Golubeva, Anna V.; Moloney, Gerard M.; Minuto, Chiara; Sandhu, Kawaljit Singh; Scott, Karen A.; Clarke, Gerard; Stanton, Catherine; Dinan, Timothy G.; Schellekens, Harriët

doi:10.1038/s41380-019-0425-1

Cited by 99 publications

(85 citation statements)

References 95 publications

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“…Classic twin studies, for example, have shown that the gut microbiota of identical twins is significantly more similar than that of fraternal twins (85). However, the main environmental factors, including diet lifestyle, evolutionary history, immune system, age, and antibiotics still influence the composition of the gut microbiota (86). The majority of studies have reported that there is a positive correlation between microbial diversity and the immune response.…”

Section: Role Of Specific Species Of Intestinal Microorganisms or Thementioning

confidence: 99%

Gut Microbiome as a Potential Factor for Modulating Resistance to Cancer Immunotherapy

et al. 2020

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Gut microbiota refers to the diverse community of more than 100 trillion microorganisms residing in our intestines. It is now known that any shift in the composition of gut microbiota from that present during the healthy state in an individual is associated with predisposition to multiple pathological conditions, such as diabetes, autoimmunity, and even cancer. Currently, therapies targeting programmed cell death protein 1/programmed cell death 1 ligand 1 or cytotoxic T-lymphocyte antigen-4 are the focus of cancer immunotherapy and are widely applied in clinical treatment of various tumors. Owing to relatively low overall response rate, however, it has been an ongoing research endeavor to identify the mechanisms or factors for improving the therapeutic efficacy of these immunotherapies. Other than causing mutations that affect gene expression, some gut bacteria may also activate or repress the host's response to immune checkpoint inhibitors. In this review, we have described recent advancements made in understanding the regulatory relationship between gut microbiome and cancer immunotherapy. We have also summarized the potential molecular mechanisms behind this interaction, which can serve as a basis for utilizing different kinds of gut bacteria as promising tools for reversing immunotherapy resistance in cancer.

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Section: Role Of Specific Species Of Intestinal Microorganisms or Thementioning

confidence: 99%

Gut Microbiome as a Potential Factor for Modulating Resistance to Cancer Immunotherapy

et al. 2020

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“…Microbiota would impact behavior via bottomup pathways, positioning it as a factor to consider in studies attempting the understanding of well-being (O'mahony et al, 2009;Dinan and Cryan, 2012;Dinan et al, 2013). Moreover, increasing evidence has posited microbiota as relevant in the context of autism (Mulle et al, 2013;Sgritta et al, 2019), schizophrenia (Severance et al, 2016), multiple sclerosis (Jangi et al, 2016), bipolar disorder (Evans et al, 2017), irritable bowel disease (Jeffery et al, 2012;Kennedy et al, 2014), obesity (Gomes et al, 2018), neurodegenerative disorders (Boehme et al, 2019), and depression (Naseribafrouei et al, 2014;Jiang et al, 2015;Aizawa et al, 2016;Kelly et al, 2016;Heym et al, 2019). The mechanisms through which microbiota exert its effects over behavior include neural pathways via the vagus nerve, regulation of the stress response, production of short chain fatty acids after fiber fermentation, amino acids metabolism and control of immune function, among others (Cryan and Dinan, 2012;.…”

Section: Gut Microbiota Influence Behaviormentioning

confidence: 99%

Measuring the Brain-Gut Axis in Psychological Sciences: A Necessary Challenge

Palacios-García

Parada

2020

Front. Integr. Neurosci.

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“…[12] Recently, Boehme and colleagues revealed a strong basal and stress-induced neuro inflammatory profile in 4 middle-aged mice, which is associated with the changes in both microbiota compositions and their metabolites. [6] Interestingly, transfer of gut microbiota from young to middle-aged subjects extended the lifespan of the short-lived killifish. [13] Studies of microbiota in midlife human are highly limited.…”

Section: Introductionmentioning

confidence: 99%

“…In aging mice model, acetate is found significantly increased in middle-aged mice compared to the older subjects, [6, 12] butyrate and valerate levels are all higher than that in young mice. [6] Prebiotics are nutrient substances beneficial to the host system through selectively digestion by gut beneficial bacteria. Inulin is one of the well-accepted prebiotics and has shown to increase the abundance of Bifidobacterium, resist pathogen colonization and modulate the host immune systems in in vitro gut model systems and humans.…”

Section: Introductionmentioning

confidence: 99%

“…[24] In middle-aged mice, feeding inulin supplementation reduces monocyte infiltration into brain and ameliorates age-related microglia activation. [6] Metabolic profiles of gut microbiota can be investigated through in vitro batch fermentation, [26] which allows large numbers of substrates and/or faecal samples to be tested quickly. [27] This method has been used in the study of inulin effect, [28] healthy modulation by inulin [29] and galacto-oligosaccharide.…”

Section: Introductionmentioning

confidence: 99%

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Age-related Changes of Microbiota in Midlife Associated with Reduced Saccharolytic Potential: An In Vitro Study

Zhu

Chen

et al. 2020

Preprint

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Background: Gut microbiota diversity and abundance are critical in maintaining human health, and subject to significantly reduce in seniors. Gut microbiota are reported to be stable across the long adulthood in general, but lack of careful examination, especially for the midlife people.Results: To characterize the gut microbiota in midlife, we investigated the faecal microbiota between two groups of healthy people, young, 20-39 years old, n=15; and midlife, 40-60 years old, n=15. Metabolic responses of the microbiota were studied through in vitro batch fermentation model. Despite no difference was observed in the diversity indies between the two age groups, a wide range taxonomic changes were found in the faecal microbiota. Furthermore, substantial Bifidobacterium reduction was also found in both faecal and fermented samples. The level of SCFAs in both faecal and starch fermented samples is similar in both groups. However, when fermentation was performed with inulin as the sole carbon source, the acetate concentration and inulin degradation rate decreased while the gas production increased in midlife group, suggesting a deficiency of saccharolytic potential in midlife, especially for non-digestible carbohydrate. Conclusions: Our data demonstrate that gut microbiota begin to change as early as in midlife. The reduction in Bifidobacterium dominates the change of the microbiota composition in midlife resulting in attenuated saccharolytic capability of inulin, leading to insufficient acetate production which might be associated with healthy problems in this transition period from young to elderly.

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Mid-life microbiota crises: middle age is associated with pervasive neuroimmune alterations that are reversed by targeting the gut microbiome

Cited by 99 publications

References 95 publications

Gut Microbiome as a Potential Factor for Modulating Resistance to Cancer Immunotherapy

Gut Microbiome as a Potential Factor for Modulating Resistance to Cancer Immunotherapy

Measuring the Brain-Gut Axis in Psychological Sciences: A Necessary Challenge

Age-related Changes of Microbiota in Midlife Associated with Reduced Saccharolytic Potential: An In Vitro Study

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