Ubiquitous Microbiome: impact on health, sport performance and disease

Microbiome Mitochondria Feedback

The gut microbiome plays a key role in regulating the optimal degree of response to exercise required to stimulate desired adaptive changes.

We have at least as many bacterial cells as human cells in our bodies. We are all familiar with the effects of disturbing the balance of beneficial microbes in our gut. Beyond this, the gut microbiome (the range of microbes, their genetic material and metabolites) is essential for health. An interactive feedback exists between gut microbiota and functional immunity, inflammation, metabolism and neurological function

Sports performance: endurance exercise increases metabolic, oxidative and inflammatory stress, signalled by the release of exerkines from exercising tissue. This signalling network induces adaptive responses mediated via the Endocrine system. Maladaptation to exercise can be due either to an undesirable over-response or an insufficient response.

Intricate interactive feedback links exist between mitochondria and the gut microbiota. In addition to being the power generators of all metabolically active cells, mitochondria produce reactive oxygen species (ROS) and reactive nitrogen species during high intensity exercise. These oxidative stress signals not only mediate adaptive responses to exercise during recovery, but influence gut microbiota by regulating intestinal barrier function and mucosal immune response. Mitochondrial genetic variation could influence mitochondrial function and thus gut microbiota composition and function. Equally, the gut microbiota and its metabolites, such as short chain fatty acids, impact mitochondrial biogenesis, energy production and regulate immune and inflammatory responses in the gut to mitochondrial derived oxidative species. So nutritional strategies to support favourable gut microbiota would potentially support the beneficial effects of the interactions described above to optimise sport performance in athletes.

Conversely, disruption to favourable diversity of the gut microbiota, dysbiosis, is associated with increase in both inflammation and oxidative stress. Not a good situation for either health or sport performance. Alteration to the integrity of the intestinal wall increasing permeability can also be a factor in disrupting the composition of the gut microbiota. The resultant increased antigen load due to bacterial translocation across the gut wall is linked to increased inflammation, oxidative stress and metabolic dysfunction. “Leaky gut” can occur in high level endurance exercise where splanchnic blood flow is diverted away from the gut to exercising tissues for long periods of time, resulting in relative hypo-perfusion and an effective re-perfusion injury on stopping exercise. In the longer term the increased levels of inflammation, oxidative stress and antigen load impair adaptation to exercise and are associated with endocrine dysfunction in chronic disease states, for example autoimmune conditions, metabolic syndrome (type 2 diabetes mellitus, obesity) and depression.

Evidence links the composition of the gut microbiota to changes in circulating metabolites and obesity. For example, low abundance of certain species of gut microbiota reduces levels of circulating amino acid glutamine, which acts as a neurotransmitter precursor. Bariatric surgery is associated with changes in the release of gut hormones regulating food intake behaviour and energy homeostasis. In addition, beneficial changes are seen in the gut microbiota which could directly or indirectly support weight loss, via action on gut hormones.

Metformin is frequency used to improve insulin sensitivity in both type 2 diabetes mellitus and polycystic ovary syndrome. However, the mechanism is poorly understood. There is now evidence that the effect of metformin is mediated via changes in gut microbiota diversity. Transfer of stool from those treated with metformin improves insulin sensitivity in mice. In addition metformin regulates genes in some gut microbiota species that encode metalloproteins or metal transporters, which are know to be effective ligands. The pathophysiology of metabolic syndrome and obesity involves an inflammatory component which is triggered by gut dysbiosis and bacterial translocation, with increased generation of oxidative species. Probiotics have a potential role in regulating the redox status of the host via their metal ion chelating ability and metabolite production, which has an impact on the production of ROS and associated signalling pathways. Prebiotics found in dietary polyphenols promote these actions of favourable gut microbiota, which is of benefit in metabolic syndrome.

Recently it has been postulated that the gut microbiome, apart from playing a crucial role in health and pathogenesis of disease states, also impacts brain development, maturation, function and cognitive processes.

Understanding the role of the gut microbiome on metabolism, inflammation and redox status is very relevant to athletes where an optimal response to exercise training supports adaptations to improve performance, whereas an over or under response in these pathways results in maladaptive responses.

For further discussion on Health, Hormones and Human Performance, come to the BASEM annual conference

Presentations

References

Endocrine system: balance and interplay in response to exercise training Dr N. Keay

Inflammation: Why and How Much? Dr N.Keay, British Association of Sport and Exercise Medicine 2017

The Crosstalk between the Gut Microbiota and Mitochondria during Exercise Front Physiol. 2017

Gut Microbiota, Bacterial Translocation, and Interactions with Diet: Pathophysiological Links between Major Depressive Disorder and Non-Communicable Medical Comorbidities Psychother Psychosom 2017

Gut microbiome and serum metabolome alterations in obesity and after weight-loss intervention Nature Medicine 2017

Metformin alters the gut microbiome of individuals with treatment-naive type 2 diabetes, contributing to the therapeutic effects of the drug Nature Medicine 2017

L’altération de la perméabilité intestinale : chaînon manquant entre dysbiose et inflammation au cours de l’obésité ? Med Sci (Paris)

Antioxidant Properties of Probiotic Bacteria  Nutrients 2017

The Impact of Gut Microbiota on Gender-Specific Differences in Immunity Front. Immunol 2017

Commentary: Dietary Polyphenols Promote Growth of the Gut Bacterium Akkermansia muciniphila and Attenuate High-Fat Diet-Induced Metabolic Syndrome Front. Immunol., 27 July 2017

Gut microbial communities modulating brain development and function Gut Microbes

 

 

Balance of Recovery and Adaptation for Sport Performance

There has been much recent discussion about the optimal balance of recovery strategies to enable effective return to training, and adaptive processes which occur as the result of training to improve sporting performance.

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I have been reading the scientific reports to try and gain an understanding of this balance between recovery and adaptation. However, my investigations were put into context after attending two fascinating meetings last week where insightful talks were given by Dr Hannah Macleod Olympic gold medallist and presentations at the King’s Sport and Exercise Medicine Conference.

The scientific principle behind exercise training, of any sort, is that improvement in exercise performance follows from the cycle of overload exercise, followed by recovery phase during which adaptive changes occur in musculoskeletal, cardiovascular, metabolic and neurological systems to improve exercise performance capacity. If sufficient recovery is not taken before next training session, then rather than a progressive stepwise upward improvement in performance capacity, a downward progression occurs. In order to avoid this overreaching and overtraining scenario, rather to improve performance, training cycle as described by Dr Macleod often consists of 3 weeks “on”, followed by “rest” week together with well structured napping.

Theoretically, if the amount of recovery needed could be shortened, then more training could be done and thus potentially more adaptive advantages gained. However, by shortening recovery time with various strategies, this might actually curtail and reduce the very adaptive changes being sought. Considering recovery and adaptive responses of skeletal muscle to exercise, there are recent apparently contradictory reports on the benefits of ice baths. To ice bath or not to? Certainly for muscle injury RICE (rest, ice, compression, elevation) regime is well established. Does the same apply for skeletal muscle recovery and adaptation post exercise? The most recent study on 9 non-elite athletic males revealed that post resistance exercise there was no difference in the inflammatory markers or cellular stress markers in skeletal muscle whether recovery was either active or with cold water immersion. Nevertheless a previous study 2015 by the same group had reported attenuated gains in muscle mass and strength with cold water immersion recovery during 3 months of resistance training in 24 non-elite athletic males. The main issue seems to be that it all depends on the part of the long term training cycle and the type of sport in which the athlete is involved. For example, during pre-season training, where long term adaptations are being sought, then an ice bath might potentially attenuate adaptive responses gained from strength training. On the other hand, in the acute clinical setting, post match in a multi-day competition, an ice bath may be of benefit during the course of this competition period. Certainly Dr Macleod described having a compressive ice system on the team bus post match during the Olympics in Rio where 8 matches were played over 14 days. So recovery, especially from any impact injuries, was far more important than considerations of longer term performance in resistance training post Olympics. Not to mention the psychological beneficial effect to athletes with reduced perception of fatigue and muscle soreness and feeling in control of all factors possible.

Finally I would also suggest that just as there is variation between individuals in the positive adaptive responses to exercise, probably genetically determined, there may also be individual variation in the extent and benefits of recovery strategies. For example, in a clinical setting, an over-response of the inflammatory pathways can actually cause harm, such as in autoimmune disease. Another point is that I have restricted this blog to discuss cellular responses of skeletal muscle to resistance exercise and competition. Clearly there are other mechanisms involved in exercise training adaptations such as the neuroendocrine system, together with other types of exercise training and other recovery strategies.

In conclusion, just as training is periodised, it would appear that recovery strategies should also be periodised in conjunction with the phase of the training /competition cycle and type of sport. Apart from the scientific rational, the psychological aspects for athletes also has to be considered.

For further discussion on Endocrine and Metabolic aspects of SEM come to the BASEM annual conference 22/3/18: Health, Hormones and Human Performance

References

“Science in Elite Sport” talk by Dr Hannah Macleod at University of Roehampton 6/12/16

“Assessing the field of play” King’s Sport and Exercise Medicine Conference, Guy’s Hospital 5/12/16

Inflammation: why and how much? Dr N. Keay, British Association of Sport and exercise Medicine 2017

Endocrine system: balance and interplay in response to exercise training

Rapid recovery versus long term adaptation

Cold water therapy and bad journalism

Do post-work out ice bath help with recovery of sore muscles?

The Use of Cryotherapy in Sports Injuries

The effects of cold water immersion and active recovery on inflammation and cell stress responses in human skeletal muscle after resistance exercise

Post-exercise cold water immersion attenuates acute anabolic signalling and long-term adaptations in muscle to strength training