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The Foundations of Lifelong Health
According to the World Health Organization (WHO), the greatest risks to lifelong health begin during the earliest stages of life. The absence of breastfeeding, unsafe water and sanitation, food insecurity, childhood infections, and further malnutrition disrupt the normal development of the infant gut microbiome and immune system. This condition is known as SAM (severe acute malnutrition) and it led to a major worldwide public health initiative in 2017 known as the Millennium Goal. These early-life factors increase the risk of infectious disease in childhood while also contributing to obesity, allergies, autoimmune disorders, metabolic disease, and other chronic conditions later in life.
Research led by Dr. Jeffrey I. Gordon, often called the father of the microbiome, has shown that improper development of the infant gut microbiome affects far more than growth. Malnutrition during this critical window can impair brain development and immune function, with consequences that follow children throughout their lives. Even after nutritional rehabilitation restores body weight, the gut microbiome often remains developmentally immature, meaning that healthy immune development depends on more than calories alone.
“Perhaps more insidious than slowing growth is malnutrition’s effect on less visible aspects of health, including impaired brain development and dysfunctional immunity, which follow these children throughout their lives”.
Dr. Jeffrey Gordon
That condition is also known as chronic dysbiosis.
Gut microbiota dysbiosis is caused by a variety of mechanisms including improper infant gut development from formula feeding, microbiome imbalance, immune dysregulation, proinflammatory mechanisms, and metabolic activities.
Dysbiosis leads to various T cell-related diseases, including:
- rheumatoid arthritis (RA)
- type 1 and type 2 diabetes,
- asthma
- cardiovascular disease
- inflammatory bowel disease (IBD)(IBD is now an umbrella term encompassing a variety of inflammatory gut related disorders)
- cancer
- liver disease
- psychiatric disorders
The World Health Organization recognizes breastfeeding, adequate nutrition, clean water, sanitation, and food security as the primary interventions for establishing a healthy start in life. Breast milk provides not only essential nutrients but also human milk oligosaccharides (HMOs), specialized carbohydrates that nourish beneficial bacteria such as Bifidobacterium longum subsp. infantis. Together, these early-life factors help educate the developing immune system, strengthen the intestinal barrier, and establish immune tolerance.
Naturally Immune For Life explores the science behind these foundational biological systems and natural oral immune therapeutics. By understanding how nutrition, the gut microbiome, and immune development interact during infancy, we can better appreciate why supporting these same biological pathways throughout life may help promote resilience, reduce chronic inflammation, and support long-term health.
In 2005, only 10% of children in the US were breastfed. Only 40% of the world’s children were breastfed in 2005.
Infant Formula Statistics
Worldwide, 59% of children receive formula milk instead of breast milk during their first year of life…..
highlighting the potential impact of formula feeding as a risk factor for highly complex necrotizing enterocolitis (NEC), one of the most severe diseases for which mortality rates have shown limited improvement over recent decades.
Although the WHO discourages bottle feeding, formula milk consumption remains common worldwide. In contrast, mother’s milk reduces the risk of NEC by factors of 6–10, as demonstrated in a multicenter cohort study of low-birth-weight infants.
The increasing global prevalence of inflammatory diseases, such as ulcerative colitis and irritable bowel syndrome, represents a challenging task for healthcare systems. Several approaches to disease management target the intestinal microbiome, which plays a key role in health and disease. One promising approach is modulating the microbiome using human milk oligosaccharides (HMOs).
Class; mammal; taxonomic group, common characteristics; mammary glands, hair/fur, and being warm-blooded.
More info:
Milk: a postnatal imprinting system stabilizing FoxP3 expression and regulatory T cell differentiation. Accumulating evidence underlines that milk is a complex signaling and epigenetic imprinting network that promotes stable FoxP3 expression and long-lasting Treg differentiation, crucial postnatal events preventing atopic and autoimmune diseases.
Clin Transl Allergy. 2016 May 12;6:18. doi: 10.1186/
s13601-016-0108-9. eCollection 2016
About galactose, an essential sugar….
Galactose is a vital monosaccharide that acts as a primary building block for cell-surface sugars (glycans). Without galactose, proper glycosylation cannot occur, meaning the immune system fails to produce the surface markers needed to recognize self-tissue, leading to a loss of immune tolerance and an inability to dampen autoimmune responses.
Why Galactose is Critical for Immune Tolerance
To understand immune tolerance, it helps to look at how the immune system “sees” the body.
Glycosylation: Galactose is an essential structural component required to build the complex sugar chains that attach to proteins and lipids (glycoproteins and glycolipids).
Self-Recognition: Immune cells use these galactose-containing glycoproteins (like specific antibodies and cell receptors) as passports. Without galactose to complete these chains, the immune system cannot properly read these “self” markers.Receptor Interaction: Immune tolerance often relies on anti-inflammatory receptors called galectins, which specifically bind to galactose-containing glycans on the surface of immune cells. When these receptors recognize the right galactose structures, they send signals that suppress overactive inflammation and induce tolerance.
How Galactose Forms Human Milk Oligosaccharides (HMOs)
Human milk oligosaccharides (HMOs) are complex, non-digestible sugars found in breast milk that act as prebiotics and immune modulators.
Galactose is the foundational building block for all HMOs.
The Lactose Core: Every HMO is built on a foundation of lactose, which is a disaccharide made of one glucose molecule and one galactose molecule.
Elongation: Specific enzymes in the mammary gland (glycosyltransferases) add additional sugar units—including more galactose and \(N\)-acetylglucosamine (GlcNAc)—to this lactose core.
Branching & Decoration: To create the vast diversity of HMO structures, these elongating chains can be further decorated with fucose and sialic acid molecules, both of which utilize galactose to anchor onto the growing sugar structure.
Remember human studies or infant studies can not be ethically done regarding the development of a human microbiome and immune system. In some rare instances specific formulas can be tried on premature infants in order to improve their chances of survival.
Source:
WHO
- Breastfeeding,
- food (security)
- and water security (sanitation)
are major protective factors against malnutrition and critical factors in the maturation of healthy gut microbiota, characterized by a transient bifidobacterial bloom before a global rise in anaerobes. Early depletion in gut Bifidobacterium longum, a typical maternal probiotic, known to inhibit pathogens, represents the first step in gut microbiota alteration associated with severe acute malnutrition (SAM). Later, the absence of the Healthy Mature Anaerobic Gut Microbiota (HMAGM) leads to deficient energy harvest, vitamin biosynthesis and immune protection, and is associated with diarrhea, malabsorption and systemic invasion by microbial pathogens. A therapeutic diet and infection treatment may be unable to restore bifidobacteria and HMAGM.
Gut microbiota and malnutrition
Worldwide, 59% of children receive formula milk instead of breast milk during their first year of life, highlighting the potential impact of formula feeding as a risk factor for highly complex necrotizing enterocolitis (NEC), one of the most severe diseases for which mortality rates have shown limited improvement over recent decades. Although the WHO discourages bottle feeding, formula milk consumption remains common worldwide. In contrast, mother’s milk reduces the risk of NEC by factors of 6–10, as demonstrated in a multicenter cohort study of low-birth-weight infants.
The increasing global prevalence of inflammatory diseases, such as ulcerative colitis and irritable bowel syndrome, represents a challenging task for healthcare systems. Several approaches to disease management target the intestinal microbiome, which plays a key role in health and disease. One promising approach is modulating the microbiome using human milk oligosaccharides (HMOs).
The resulting economic burden is substantial, with estimates for annual direct healthcare costs in Europe ranging from €900 to €2100 [6] per patient with IBS and annual direct healthcare costs ranging from €2000 to €3500 per patient with ulcerative colitis or Crohn’s disease, respectively.
We further explored this association and demonstrated that the microbiome has a causative component in ulcerative colitis [21], which is a noncommunicable disease. This complex disease is influenced by many factors; we were able to transfer the phenotype of ulcerative colitis via the gut microbiome from diseased to healthy individuals in a mouse model. Current knowledge suggests a more complex scenario, which includes not only the microbiome and its direct effects on gut functions but also the bidirectional interaction between the host and its microbiome, which results in a balanced system in healthy individuals.
Orally administered medicine:
WHO (Levine and Dougan, 1998; Neutra and Kozlowski, 2006; Bermúdez-Humarán et al., 2011).
Currently available treatments for IBD, which target the systemic immune system, induce immunosuppression, thereby exposing the patient to the risk of infections and malignancy.
A dysfunctional autophagic mechanism leads to chronic intestinal inflammation in IBD.
Both gut microbiota and food-derived antigens alter intestinal DCs function, and contribute to a loss of tolerance and to induction and progression of IBD.19 In patients with IBD, the tolerance/immunity balance is disturbed, leading to chronic intestinal inflammation driven by aberrant T-cell reactivity to intestinal bacteria. Tolerogenic DCs act by promoting differentiation and expansion of Tregs that efficiently modulate gut inflammation, and they are disturbed in IBD.
The lamina propria constitutes an effector site that actively influences Tregs-cell function. Tregs must be in the proximity of their target cells within lymphoid organs and the lamina propria in the intestine. Foxp3(+) Tregs maintain immune balance in the gut via IL-10- and TGF-β-dependent mechanisms. Their differentiation and function are modulated by intestinal microbiota. Inflammation in IBD is mediated by inappropriate production of pro-inflammatory cytokines by CD4+ T-effector cells, which are not suppressed by Tregs. Activation of Tregs inhibits the inflammatory response to commensal bacteria and is central for mucosal tolerance. Loss of this mechanism leads to inappropriate immune reactivity toward commensal organisms, contributing to mucosal inflammation in IBD.
Th17 cells infiltrate the intestine of IBD patients, producing IL-17 and amplifying the inflammatory process. Th17 can be converted into either IFN-γ-producing Th1 cells or Tregs. Antigen presenting cells mediate differentiation of naive T cells into effector T-helper cells, including Th1, Th2 and Th17, and can alter gut homeostasis leading to IBD.
Macrophages functions change during infection and inflammation. The intestinal macrophage pool requires continual renewal from circulating blood monocytes, unlike most other tissue macrophages, which derive from primitive precursors that subsequently self-renew. Macrophages in the gut have a role in Tregs function. As regulatory cells in the gut, macrophages also have a role in the pathogenesis of IBD.
The function of both T and B cells is required for proper interplay between the gut and the systemic immune systems. Plasticity of CD4+ helper T cells is important for the correct function of the gut immune system.
Dysbiosis and alterations in the intestinal microbiome are associated with IBD. Gut microbes can induce and sustain the disease. The loss of normal tolerance to intestinal microbiota and/or to food or environment-derived antigens leads to mucosal damage.
On the basis of the above, fecal transplantation was developed as a mean for the treatment of IBD.
Taken together, these studies suggest that each of the components of the gut immune system is pertinent for the induction and/or progression of IBD. Most of these subsets of cells are involved directly or indirectly in the signaling between the gut and the systemic immune systems, a process that is relevant for the generation and maintenance of the inflammatory process in IBD. Therefore, oral immune therapy, which affects these types of signals between the gut and the systemic immune systems, may aim at several of these targets.
Gastroenterology and Liver Units, Department of Medicine, Hebrew University-Hadassah Medical Center, Jerusalem, Israel
Clinical & Translational Immunology (2016)
Kwashiorkor
Kwashiorkor is a form of acute malnutrition, and it seems to be caused by environmental factors and a lack of protein in the diet. Recently, the team of Prof. Gordon at WUSTL established that the microbiome is one of the causal factors in this disease. This is one of the few cases in which we have advanced enough to have established a “bad microbiome” to be one of the causal factors of a disease. Granted, it is not the only factor, but it is one of them rather than just a marker of the disease. NIH’s medline on Kwashiorkor Smith et al., 2014, Gut microbiome of Malawian twin pairs discordant for kwashiorkor.
Abstract: Kwashiorkor, an enigmatic form of severe acute malnutrition, is the consequence of inadequate nutrient intake plus additional environmental insults. To investigate the role of the gut microbiome, we studied 317 Malawian twin pairs during the first 3 years of life. During this time, half of the twin pairs remained well nourished, whereas 43% became discordant, and 7% manifested concordance for acute malnutrition. Both children in twin pairs discordant for kwashiorkor were treated with a peanut-based, ready-to-use therapeutic food (RUTF). Time-series metagenomic studies revealed that RUTF produced a transient maturation of metabolic functions in kwashiorkor gut microbiomes that regressed when administration of RUTF was stopped. Previously frozen fecal communities from several discordant pairs were each transplanted into gnotobiotic mice. The combination of Malawian diet and kwashiorkor microbiome produced marked weight loss in recipient mice, accompanied by perturbations in amino acid, carbohydrate, and intermediary metabolism that were only transiently ameliorated with RUTF.
Gut Microbiomes of Malawian Twin Pairs Discordant for Kwashiorkor
Since the evolution of the mammalian birthing process must be adaptive, its disruption may prevent natural development of the neonatal microbiome and increase neonates’ long-term risk of metabolic and immune diseases. In light of this, elevated rates of C-section delivery, pre- and perinatal antibiotic use and formula feeding underscore the importance of promoting vaginal delivery and more conservative….
Vaginal delivery and breastfeeding are evolutionarily adaptive for mammals and therefore are paramount to human newborn development and health. Common perinatal interventions like C-section, antibiotic use, and formula feeding alter the infant microbiome and may be major factors shaping a new microbiome landscape in human history. While mechanistic questions remain, epidemiological evidence suggests that these impacts on the early microbiome assembly are associated with metabolic and immune disorders.
The infant microbiome development: mom matters
The Risks of Not Breastfeeding for Mothers and Infants
Immune Tolerance aka Checkpoint Blockade Toxicity
Immune tolerance, or immunological tolerance, or immunotolerance, is a state of unresponsiveness of the immune system to substances or tissue that have the capacity to elicit an immune response in a given organism. The Th1 cytokine profile is vital for clearance of certain organisms and ancillary immune activity, and a limiting effect on this cytokine profile may result in reduced chances for overcoming infections especially intra-cellular organisms residing within macrophages. Effective clearance will depend on appropriate macrophage activation (which occurs through IFN≥ release by Th1 and NK cells) and production of nitric oxide. If this pathway is disrupted IFN≥ secretion is blocked, impairing macrophage activation. Persistent blockade of these inhibitory receptors has lead to the breakdown in immune self tolerance, thereby increasing susceptibility to autoimmune or auto-inflammatory side effects, including rash, colitis, hepatitis and endocrinopathies. Many drugs may cause checkpoint blockade toxicity including pharmaceutical drugs termed ‘immuno therapy’ by pharmaceutical companies, these include Mab drugs and cancer treatments.
Checkpoint Inhibitor–Induced Colitis: A New Type of Inflammatory Bowel Disease? Madeline Bertha, MD MS, corresponding author1 Emanuelle Bellaguara, MD, Timothy Kuzel, MD, and Stephen Hanauer, MD ACG Case Rep J. 2017; 4: e112. Published online 2017 Oct 11. doi: 10.14309/crj.2017.112 PMCID: PMC5636906 PMID: 29043290
Checkpoint Inhibitor-Induced Colitis: A New Type of Inflammatory Bowel Disease
Dysbiosis & FMT
Gut microbiota dysbiosis is caused by a variety of mechanisms including improper infant gut development from formula feeding, microbiome imbalance, immune dysregulation, proinflammatory mechanisms, and metabolic activities.
Dysbiosis leads to various T cell-related diseases, including:
- rheumatoid arthritis (RA)
- type 1 and type 2 diabetes,
- asthma
- cardiovascular disease
- inflammatory bowel disease (IBD)(IBD is now an umbrella term encompassing a variety of inflammatory gut related disorders)
- cancer
- liver disease
- psychiatric disorders
Current Research Limitations
Despite the importance of understanding microbiome-T cell interactions, most immunology experiments have been performed with limited microbiome composition such as specific pathogen free (SPF) or germ free (GF) mice. Experimental results using gnotobiotic, that is specific colonized mouse models in the drug development stage cannot fully represent humans. To address these limitations, a fecal microbiota transplant (FMT) mouse model with a gut microbiota similar to that of humans was developed using human or wild mouse feces. The FMT mouse model has an abundant and more diverse gut microbiome than current experimental animal models. Mice implanted with the wild mouse or human microbiota not only exhibit different degrees of microbial diversity but their systemic immunity is also affected.
Microbiota Plays Critical Role in Immune Disorders
The need to shed light on the unknown aspects of pathophysiology of common disorders, such as gastrointestinal ones, has led researchers through last decades to study and define the role of microorganisms within the human intestine and their interactions with the host. The progress of technology has permitted the overcoming of culture-based methods to study microbes and paved the way to molecular techniques, which allow the analysis of microbial genome, microbial functions, and metabolism. These progresses opened a window on the world of microbiology and permitted to deepen into the key role played by gut microbiota and dysbiosis in health status and diseases, both gastrointestinal and extraintestinal. So, scientists focused their attention in developing new strategies to restore eubiosis and to manipulate gut microbes by modifying dietary habits, administrating antibiotics, probiotics, and prebiotics and using fecal microbiota transplantation as treatment of gastrointestinal, infectious, cardiovascular, metabolic, immune-mediated, neuro-psychiatric, and oncological disorders. The next challenges will be to elaborate standard protocols with definite outcomes predictors in disease-specific settings.
From Regular Catharsis with Castor Oil to Recognizing the Importance of the Intestinal Microbiota
Milk: a postnatal imprinting system stabilizing FoxP3 expression and regulatory T cell differentiation. Accumulating evidence underlines that milk is a complex signaling and epigenetic imprinting network that promotes stable FoxP3 expression and long-lasting Treg differentiation, crucial postnatal events preventing atopic and autoimmune diseases.
Clin Transl Allergy. 2016 May 12;6:18. doi: 10.1186/
s13601-016-0108-9. eCollection 2016
The 2025 Nobel Prize in Physiology or Medicine has been awarded to Mary Brunkow, Fred Ramsdell, and Shimon Sakaguchi ‘for their discoveries concerning peripheral immune tolerance’. The award honours the discovery of a unique subset of immune cells – Regulatory T cells (Tregs) – which differ fundamentally from most immune cells that typically promote inflammation. In contrast, Tregs suppress immune activation, maintain immune homeostasis, and prevent immune-mediated tissue destruction. Without Tregs, the immune system fails to regulate itself, leading to catastrophic multi-organ autoimmunity.
Regulatory T cells: the 2025 Nobel prize in physiology or medicine
Immune For Life
M. Ferrari
After decades of chronic health conditions and serious gut issues like IBS and SIBO, immune deficiencies and an autoimmune condition discover how I recovered my health thanks to natural oral immune therapeutics (maf and gcmaf). Due to a premature birth and being formula fed, I was a SAM child in real life. My book is a step by step journey you won't want to miss that illustrates how to regain or maintain health for all ages.