In Evolution, context is everything. Survival of the fittest is contingent upon available options inherited from survivors of past circumstances. No perfect design suited for ever changing conditions has yet been identified, and nobody works alone. Oftentimes, fitness goes to those who best work within the confines of their environment, taking what is necessary, leaving the rest to manage on their own, and cooperating to achieve mutually beneficial outcomes whenever possible.
All of this happens as we are immersed in world of microbes. We have evolved to spend our entire lives with these unseen cohorts. Microbes assist and challenge us from cradle to grave. They give us as much as they take, as long as we can take it. Only now are we starting to develop an understanding of the multifaceted mosaic of our relationships with diverse microorganisms. A major portion of these relationships deals with those microbes that live in direct contact with our bodies. We need many of them in order to live out healthy and productive lives. As a collective, this set of organisms is known as the human microbiome.
The microbiome varies among individuals, with some of these differences now being associated with a variety of diseases and syndromes. We are coming to realize that good nutrition, healthy bodies and positive emotions rely on good relationships with specific microbiota. Failure to establish or disruption of these interactions might lead to any of a number of physical or psychological problems, depending on the specific broken relationship.
In this chapter, details on some of the latest findings concerning the human microbiome will be outlined. Research in related topics is exploding. Over the last 20 years, the number of scientific microbiome reports published annually has increased over a hundred fold. There is too much to cover all of it here. It is also too early to determine which areas of microbiome research will prove to be most informative and important. Nevertheless, there is enough information available at this time to conclusively demonstrate that the human microbiome is extremely important to each of us. I hope that these examples herein accurately and properly convey the significance of our relationships with our microbiomes, at least as a rough sketch drawn as based upon our current knowledge.
Gut microbes participate in digestion and metabolism
Perhaps the most obvious place to look at our microbiome is in our guts. It’s well known that we carry around all kinds of passengers in our digestive systems. Now, we are coming to realize how important they are for digestion and metabolism.
We give them a place to live and bring them food, and in exchange, our microbiomes help us digest our food, produce vitamins, and prevent pathogens from gaining footholds. They break down excesses that escape our digestive enzymes, and they have on the order of a thousand times more enzymes than we do to break down almost anything that enters our guts.
The best example among these organisms is Bacteroides thetaiotaomicron that is endowed with a genome that codes for over 260 hydrolases, which is far more than the number encoded by the human genome.
Among the compounds they break down are complex secondary metabolites and toxic xenobiotics, which adds to our digestive repertoire and protects us from poisoning. On the other hand, they also metabolize drugs, which complicates formulating which drugs to prescribe and how strong of dosages to take.
Given the direct connection between the microbiome and metabolism, it’s a small step to link gut microbiota with metabolic syndrome issues.
Metabolic syndrome is defined by a clustering of metabolic disorders that include central adiposity with visceral fat accumulation, dyslipidemia, insulin resistance, dysglycemia and non-optimal blood pressure levels. Metabolic syndrome is associated with an increased risk of cardiovascular diseases and type 2 diabetes...Existing evidence from studies both in animals and humans support a link between gut microbiome and various components of metabolic syndrome.
As usual, the story is not so simple. There are many complicating factors and results are not always consistent, so much remains to be learned. For example, links between obesity and components of the gut microbiome have been suggested. However, a systematic review of publications reports inconsistent results and problems with methodologies that make it difficult to draw overarching conclusions.
The gut connects to the brain
It’s more than getting cranky when you’re hungry. Recent research is outlining multiple lines of bidirectional biochemical and neurological communication between the gut and brain.
Within your body, regular communication occurs between your gut and brain through neuronal signals, along with chemical messaging between tissues involving neurotransmitters (GABA, 5-HT), hormones (peptide YY), short chain fatty acids (SCFAs), and immune system signaling compounds (cytokines). Dysbiosis, i.e. disruption or imbalance of the microbiome, in the gut is associated with a variety of detrimental outcomes.
Recent reviews by Stefano, et. al, Lombardi et. al and Liang, et. al have outlined the relevance of a number of these gut-brain axis interactions for understanding neurodegenerative and psychiactric disorders. The foundation of the gut-brain axis is built within the context of a core set of archetypal chemical messengers that allows for the evolution of complex cellular systems and communication between interacting organisms. With this ability to communicate, disparate organisms can live together in coordinated and mutually beneficial communities that reaches to the level of neurological functioning and mental health. The result is that our health and well being have come to rely on microbial assistants.
The interface between us and our gut microbiota is the epithelial lining of our digestive system. Humans have evolved complex systems geared to monitor, maintain and protect this interface. Disruption of the microbial community and/or of the epithelial lining can lead to inflammation responses and leakage of toxic chemicals into the circulatory system. That’s not good for us.
the putative pathophysiological role of environmentally determined deficiencies of dietary components on altering essential ratios of human gut microbiota … appears to be intimately associated with pro-inflammatory processes underlying IBS (irritable bowel syndrome) and PD (Parkinson’s disease) progression
Liang et. al detail how the gut-brain axis is also an important component of depression.
The pathophysiology of major depression has been increasing clearly following the development of neuroscience and bioinformatics. It mainly involves four aspects, the dysfunction of the brain, the hypothalamus–pituitary–adrenal (HPA) axis, the immune system, and the gut–brain axis.
Beyond these linkages, a number of potential connections between the microbiome and neurological maladies are suggested in emerging studies. Liang, et. al describe reports of the influence of microbiome disruptions on the progression of multiple sclerosis and Alzheimer’s disease. Stefano, et. al describe mounting evidence for associations between gut microbiota dysbiosis and a range of other problems, including affective spectrum disorders and psychiactric disorders. Moreover, inflammatory responses resulting from imbalances in the gut microbiome can cross the placenta and lead to cognitive impairment and behavioral disorders in offspring. Evidence that these associations might be important is supported in initial reports on the beneficial effects of interventions such as consumption of prebiotics (chemicals used to manipulate the microbiome), probiotics or fecal microbiota transplant (FMT).
Protection against infection and modulation of the immune system
While a handful of microorganisms provide assistance to us in our microbiomes, many others are constantly seeking to invade and overrun our defenses. These defenses include complex networks of interacting components that can be generally categorized as either innate or adaptive defense responses.
Though it is too complex to outline here, suffice it to say that the human microbiome modulates both innate and adaptive immune responses. Furthermore, it seems that proper establishment of a microbiome early in life might be important for regulating immune responses through adulthood.
(R)eductions in four bacterial genera at 3 months of age was associated with an increased risk to develop asthma at one year of age...(O)ut of three compositionally distinct neonatal gut microbiotas identified in a US birth cohort, those children that harbored a gut microbiota with lower relative abundance of key bacteria ... and increased abundance of some fungi, had the highest risk for developing atopy against multiple food and aeroallergens at 2 years of age
In other words, asthma and allergies might result from imbalances in the microbiome, at least for some people. Interestingly, recent reports suggest that chronic respiratory ailments can be alleviated through probiotic treatment, and inhaling them through the nose might be better than eating probiotics for chronic respiratory ailments.
Conclusions
This review, while long, barely scratches the surface of progress in understanding the human microbiome. The more we look, the more we find how much we owe to the community of microbes that live in and on us. A healthy microbiome imparts many benefits to the human host. Meanwhile, dysfunction in the microbiome leads to many negative consequences for us. In short, our microbiota are integral to our existence. They will not be replaced by any synthetic substitutes any time soon.
Increasing understanding of our microbial cohorts raises many issues with how we previously perceived microbiology, our relationships with microbes, and how we attempt to manipulate this community. We can no longer simply write off bacteria as germs to be killed wherever possible. Neither are they simple machines to exploit for single purposes, such as fermentation. Humans have evolved with a bacterial baptism through vaginal birth. Cesarean births might benefit from simulating this process. After birth, breastfeeding seeds infant microbiomes. As we develop and age, we need to add microbiome health to our concepts of diet and exercise for a healthy life. Junk food affects us and our microbial community, which might not simply recover with exercise. It also means that we must incorporate the microbiome into risk-reward calculations for using antibiotics and other interventions that can perturb the community. Finally, there are many subjects that could not be covered here. Examples include skin conditions, cancer risk and potential treatments that are being studied through the lens of the microbiome.
To be clear, human physiology and genetics are also important factors in health and well being. Environmental stress can impact genetically predisposed individuals regardless of the microbiome. Exercise is still important no matter what is in our guts. And, somehow living a life with purpose has overriding impacts on well being. The keys to our health include myriad interacting internal and external factors that we only partially understand. The microbiome is important, but still only part of the picture.