Gut health and chronic disease (Part II): Our gut biome's co-workers and their role in resilience

How our myriad microbiomes connect to the gut, and why understanding them all is crucial to shaping our disease risk and resilience.

Sep 07, 2025

In Part 1, we explored the gut as a central hub for digestion, immunity, metabolism, and mood. In this next publication, we are zooming out: the gut is not an island, but part of a vast microbial ecosystem that spans the entire body.

When we talk about gut health, it’s easy to reduce the conversation to a tally of “good” and “bad” bacteria. But the reality is far richer and far more important for understanding health and disease. A key distinction sets the stage: microbiota refers to the living organisms themselves—bacteria, fungi, viruses, archaea, even parasites. Microbiome, on the other hand, includes not only those organisms but also their genetic potential (genes), their chemical fingerprints (metabolites), and the jobs they perform within the body (functions).

This shift in perspective moves us away from a numbers game toward viewing the gut as an ecosystem. Health emerges not from the sheer presence or absence of certain microbes, but from the overall harmony and productivity of that system. Disease, then, is less about invaders and more about lost functions, imbalances, or toxic byproducts. And therapies become not just about wiping out or adding microbes, but about restoring balance at the system level, where resilience truly resides.

Distinct microbial communities populate nearly every surface and cavity of the human body, each with specialized roles in maintaining balance and constant communication with one another. To see this web of influence in action, let’s take a closer look at the hub-and-network dynamics of specific microbiomes and how they shape the gut.

The oral microbiome: gateway to systemic health

Saliva and swallowed bacteria provide a direct route for oral microbes into the gastrointestinal tract, influencing gut composition. Conversely, gut inflammation and systemic immune signals can alter the oral microbial environment, explaining bidirectional links between periodontal disease and gut dysbiosis. For practitioners, this cross-talk underscores the importance of considering oral health when addressing digestive concerns with clients and patients. Our oral microbiome includes hundreds of bacterial species that help regulate the mouth’s pH, begin digestion, and maintain tooth and gum health. Beyond oral health, this community acts as a gateway to systemic health: when balanced, it limits colonization by pathogens; when disrupted, it can seed inflammation elsewhere in the body.

Why it matters: Oral pathogens and chronic inflammation don’t just stay in the mouth. They are swallowed daily and travel to the gut and beyond, altering microbial composition. Chronic oral inflammation also increases systemic inflammatory markers, such as CRP and cytokines, which can increase gut permeability, leading to greater immune activation and increased risk for cardiovascular disease and diabetes. New research also highlights a link to Alzheimer’s, suggesting a direct connection between oral health and brain function.

The vaginal microbiome: hormones and protection

The vaginal microbiome is one of the best examples of microbial specialization. Dominated by Lactobacillus species, it produces lactic acid that maintains a low pH environment, offering protection against pathogens and supporting reproductive health. This balance is dynamic, influenced by hormonal shifts across the lifespan. During reproductive years, Lactobacillus dominance supports fertility and pregnancy outcomes, while menopause reduces glycogen availability in vaginal tissues. In perimenopause and menopause, this shift is significant because it contributes to Genitourinary Syndrome of Menopause (GSM), weakens microbial stability, and increases the risks of inflammation and infection. These microbial dynamics are strongly influenced by hormones and immune status, meaning that disturbances in gut ecology can directly impact vaginal balance.

Why it matters: Disruptions in the vaginal microbiome increase risk of bacterial vaginosis, preterm birth, and infertility. Imbalances in this area are often overlooked in broader discussions of microbiome science.

The skin microbiome: where inside meets outside

The skin microbiome illustrates how external and internal systems meet. It produces antimicrobial compounds, supports wound healing, and trains the immune system. Yet, it is also sensitive to gut-derived metabolites and inflammatory signals. Gut dysbiosis can exacerbate skin conditions, including eczema and acne. In practice, this suggests that persistent dermatological complaints may warrant an assessment of gut health and diet as part of a broader strategy.

Why it matters: Skin dysbiosis reflects immune dysfunction that often originates in gut imbalance, but it also works in reverse. Chronic skin inflammation increases systemic cytokine levels, which stress the gut barriers and alter microbial communities. This bi-directional loop helps explain why many people with eczema or psoriasis also have GI complaints or autoimmune comorbidities.

The lung microbiome: gut-lung axis

The lung microbiome, once assumed sterile, is now recognized as a low-biomass but active community. It interacts with the gut via the gut-lung axis, where microbial metabolites and immune signals travel between the two systems. A balanced lung microbiome appears to support immune readiness and tolerance, while disruption is increasingly associated with asthma, COPD, and chronic infections. Clinically, this means that respiratory and digestive symptoms may be more effectively addressed together rather than in isolation.

Why it matters: In asthma, airway inflammation alters immune signaling. Those same immune pathways, especially Th2 skewing and cytokine release, influence gut immunity. Studies show that asthmatic inflammation can alter the gut microbial balance, reducing the number of beneficial species and weakening tolerance. That, in turn, heightens the risk of allergic disease, metabolic dysfunction, and other chronic inflammatory conditions.

Other biomes: liver, bladder, brain

Even organs not traditionally considered microbially active exhibit microbial influences. The liver, pancreas, and gallbladder are indirectly shaped by gut-derived metabolites through portal circulation, which impacts energy metabolism and detoxification. The bladder harbors a low-biomass microbiome that contributes to urinary tract health, influencing susceptibility to infection and chronic irritation.

The brain itself does not have a resident microbiome, but it is deeply connected through the gut-brain axis, receiving constant input from gut microbial signals that affect neurotransmission, stress responses, and cognition. The gut-brain axis (GBA) is a central component of the body’s microbial network and illustrates how gut health impacts not only digestion and immunity but also mood, cognition, stress responses, and sleep. Microbial metabolites, neurotransmitter precursors, and immune signals travel from the gut to the brain, while the brain regulates gut function through hormones and autonomic pathways. By incorporating bidirectional communication into the discussion of microbial networks, we can gain a deeper understanding of the broader significance of gut health and its central role in whole-body resilience.

Of course, the gut-brain axis

By now, most people have at least heard of the GBA. It is often mentioned in conversations tied to mood, stress, or digestion. What it really describes, however, is a sophisticated, two-way communication system between the gut microbiome and the brain. Signals travel along multiple channels. The vagus nerve provides a direct neural line, carrying information from the gut to the brain in real time. Hormones add another layer: gut microbes help shape cortisol and gut peptides that regulate stress, appetite, and mood. The immune system is also deeply involved, as microbial metabolites influence the release of cytokines that can alter brain function and behavior.

When this system is in balance, it supports mental clarity, emotional regulation, and resilience. When it’s disrupted through dysbiosis or imbalance in the gut community, the ripple effects can show up in ways that look very different on the surface: depression, anxiety, autism spectrum disorder, even neurodegenerative conditions like Alzheimer’s and Parkinson’s.

Why it matters: These body-wide microbial systems remind us that health is a networked property. The gut may be the hub, but each microbial community contributes unique and essential functions to overall resilience.

Shared microbial language

Despite their different locations and roles, the body’s microbiomes communicate in a common biochemical ‘language’ to sustain health. They metabolize dietary compounds into short-chain fatty acids (SCFAs) and other metabolites that fuel colon cells, shape immune tolerance, and influence energy metabolism. They also provide colonization resistance, producing antimicrobial compounds that keep harmful organisms in check.

This shared set of functions is what links the oral, skin, lung, vaginal, and other microbiomes back to the gut. Signals from one community travel into the others through circulation, immune pathways, and the nervous system. In this way, the body’s microbial ecosystems act less like isolated neighborhoods and more like an interconnected network, each speaking the same language, each influencing the others.

Why our gut matters the most

Among all these interconnected microbial communities, the gut stands out as the most dense, diverse, and influential hub. It not only carries the richest microbial population but also sits at the crossroads of digestion, metabolism, immunity, and brain signaling. Colonization begins at birth, shaped by delivery mode, breastfeeding, antibiotic exposure, and environment. Vaginal delivery and breastfeeding promote colonization with Lactobacillus and Bifidobacterium, while diverse exposures in early childhood expand microbial richness. In contrast, cesarean delivery tends to favor colonization by skin-associated and environmental microbes, often reducing microbial diversity and increasing the risk of allergies, autoimmune disorders, and metabolic diseases later in life. An overly sanitized environment can also limit microbial diversity and increase the risk of immune-mediated disease.

The gut microbiome contributes directly to digestion and metabolism by fermenting fiber into SCFAs, regulating nutrient absorption, and supporting systemic energy balance. It communicates with mitochondria, influences immune training, and constantly signals to the brain through neural, endocrine, and immune pathways. Keystone species are particularly important within the gut microbiome, exerting influence beyond their relative abundance. For example:

Bacteroides and Prevotella both play central roles in breaking down complex carbohydrates and fibers.
Faecalibacterium prausnitzii is a major producer of butyrate, which fuels colon cells, maintains the gut barrier, and reduces inflammation.
Akkermansia muciniphila resides in the mucus lining of the gut, strengthening this barrier and supporting metabolic health.
Bifidobacterium species are among the earliest colonizers of the infant gut, feeding on human milk oligosaccharides, and throughout life, they continue to support the integrity of the gut barrier and immune responses.
Lactobacillus species help maintain mucosal pH through lactic acid production, inhibiting pathogens and promoting balance.
Roseburia and Ruminococcus degrade complex fibers and generate beneficial SCFAs. When these species decline, the result is not only local inflammation but also systemic consequences that extend to the lungs, skin, and oral cavity.

In conclusion

The future of microbiome science lies in personalization and integration. Advances in sequencing now make it possible to map microbial “fingerprints,” enabling tailored diets and targeted interventions. The “old friends’ hypothesis” reminds us that humans co-evolved with environmental microbes that trained immune tolerance, organisms largely missing from modern life. Reintroducing their signals, whether through diet, lifestyle, or supplementation, may help restore balance.

Most importantly, the gut must be understood in context. It is a powerful hub, but it cannot be separated from other microbial communities. Oral, vaginal, skin, lung, and other biomes each bring unique roles, and their constant cross-talk with the gut ensures that an imbalance in one reverberates across the whole. For practitioners and health seekers, the takeaway is actionable: gut health matters, but only as part of a whole-body biome network. Recognizing this interconnectedness shifts both science and practice toward true whole-person care.

If you are enjoying this series on gut health and chronic disease, please like and subscribe to stay tuned for more great information on this very topic. Next, we tie Part I and Part II together to form actionable approaches for building resilience.

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