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Immune balance: The compelling link between HRB probiotics and the immune system

Immunity is the main mechanism of host defence against infectious agents. It functions to protect us from foreign invaders and the illnesses they cause. To function well, it requires balance and harmony. There is, in particular, a public interest on improving immune system these days. The popularity, among consumers, of how to improve the body’s immune system has contributed to an increased demand for immunomodulating nutritional supplements. While the idea of boosting your immunity is enticing, having an optimally functioning immune system is more important for healthy living.

Modulation of the gut microbiota with probiotics supplementation appears as a feasible approach for immune health. Our immune system has co-evolved along with a diverse gut microbiota, a forgotten organ that until recently has been largely overlooked. The gut microbiota plays a key role in the development and maintenance of immune system. In fact, approximately 70-80% of the immune cells are located in the gut – specifically, within the inside lining of the intestines. Alteration of gut microbiota balance, a state termed dysbiosis, is inextricably linked to several highly prevalent health disorders including inflammatory bowel disease (IBD), irritable bowel syndrome (IBS), colorectal cancer, allergy, and chronic diseases such as type-2 diabetes and obesity.   


Human-residential bifidobacteria: Natural inhabitant of the human gut

Bifidobacterium ​is thought to be a keystone taxon in human gut microbiota that plays crucial roles in regulating immunological and physiological functions. Their presence in the human intestine are being purported as beneficial for human health.

In addition to the presence in the human gut, bifidobacterial species also naturally occur in a range of ecological niches such as animal intestines, sewage, and foods. Accumulating evidence shows that bifidobacteria have coevolved with their respective hosts and could be categorised into two major groups; those that naturally reside in human intestines are called human-residential bifidobacteria (HRB), whereas others who are the natural inhabitants of animal intestines or environment are regarded as non-HRB1​ (Figure 1).

Figure 1

Figure 1. ​Ecological distribution of bifidobacterial species.


Accumulating evidence shows that HRB possess numerous unique physiological characteristics, which non-HRB do not have, contributing to their beneficial roles in promoting human health (Table 1). In fact, only those HRB species, commonly found in the infant gut microbiome, can utilise the oligosaccharides (HMOs) and tolerate the antibacterial factor (lysozyme) found in human breast milk2,3​. In addition, HRB are superior to non-HRB at producing folate4​, a critical cofactor for cell growth and metabolism, and certain HRB species are particularly effective at eliminating potentially harmful food-derived opioid peptides5​. New research also discovered that certain strains of HRB have a better functional capacity at producing indole-3-lactic acid6​, a unique metabolite that is involved in infant immune and neuronal development7​.

Table 1. Different physiological properties of HRB and non-HRB.

Table 1


Morinaga Milk has developed a premium line of probiotic strains that are highly compatible with the human gut. The four main HRB probiotic strains are B. longum ​subsp. longum ​BB536, B. breve ​M-16V, B. longum ​subsp. infantis ​M-63, and B. breve ​B-3, all of which are from the gut of infants and possess a proven record of safety and clinical efficacy on human health (Figure 2).

Figure 2

Figure 2.​ Morinaga Milk’s HRB are ideal probiotics for human use.

Infancy: HRB on immune development


The first 1,000 days of life represents a window of opportunity for shaping a healthy gastrointestinal tract and immune system, affecting lifelong health. During this critical period, the infant’s gut microbiota is developing along with its immune system. Bifidobacterium ​is one of the most dominant bacterial genus present in the healthy gut. Colonisation with bifidobacteria is believed to play pivotal roles in the maturation of the immune, digestive and metabolic systems, which, in turn, protect against the susceptibility to various diseases later in life.

Insufficient or aberrant colonisation of bifidobacteria during the critical neonatal period, which is often affected by factors such as gestational age, delivery mode, and feeding types, may lead to an exaggerated adaptive immune response and reduced tolerance, and, in turn, precede the development of immune-related health complications such as necrotising enterocolitis (NEC), allergies, eczema, etc8​.

Positive modulation of gut microbiota with Morinaga Milk’s HRB probiotics during this critical period has shown promising beneficial effects against immune-mediated and microbiome-related health complications. One great example is B. breve ​M-16V9​. Early administration of B. breve ​M-16V improves bifidobacterial colonisation in premature infants and reduces the risk of developing NEC and sepsis. Clinical evidence and mechanistic studies revealed that B. breve ​M-16V could improve the gut barrier function, assist mucosal immunity development by stimulating transforming growth factor-beta (TGF-β) signalling and attenuate inflammatory reactions by modulating the expressions of toll-like receptor 2 (TLR2) and TLR4.

B. breve ​M-16V could also be a potential approach to improve immune tolerance and protect infants against allergic disorders, including atopic dermatitis (eczema), food allergy, allergic rhinitis and asthma. Administration of B. breve ​M-16V could promote bifidobacterial colonisation, modulate Th2-skewed immune response and attenuate inflammatory reactions.

Other Morinaga Milk’s HRB probiotics also show promising beneficial effects on the immune health of infants. When combined, Morinaga Milk’s HRB probiotics work even better as a team. Prenatal and postnatal administration of a probiotic mixture containing B. longum ​BB536 and B. breve ​M-16V is tied to lower risk of allergic disorders in infants later in life, up to 1.5 years. The combinatory Triple Bifidus probiotics (B. longum ​BB536, B. breve ​M-16V, and B. infantis ​M-63) have shown to exert triple synergistic effect that promote early colonisation of bifidobacteria in infants and help prevent the development of infections and allergic disorders. 

Adulthood: HRB on immune health


It is increasingly evident that a healthy interaction between the immune system and the gut microbiota is crucial for the maintenance of the body’s homeostasis and health. Lifestyle in this modern era – stress, poor diet, and the regular use of antibiotics – can affect the microbiota composition and possibly lead to an imbalance in the immune system. Reduction of beneficial commensal bacteria is closely related to skewed T cell responses and the induction of immune-mediated disorders such as allergy, cancer, and infections.

Morinaga Milk’s HRB probiotics have shown to confer positive benefits on immune health in adults. Clinical studies have shown that the HRB strains B. longum ​BB536 and B. breve ​M-16V can positively modulate the immune response and ameliorate allergic reactions in healthy adults. In particular, B. longum ​BB536, the most well documented HRB probiotic strain, possesses a strong immunomodulatory function for prevention and amelioration of immune-mediated disorders10​.

Administration of B. longum ​BB536 promotes the stabilisation of gut microbiota and increases the abundance of bifidobacteria, which consequently restores Th1/Th2 immune balance and dampens allergic reactions in adults. It is also evident that B. longum ​BB536 can not only augment host immunity against cancer but can also restore immune balance and inhibit inflammation in adults by driving a fine-tuned homeostatic balance within the host-microbiome interaction.  

In addition, altered gut microbiota are associated with the metabolic syndrome, occurring in most obese individuals. Gut microbiota may contribute to the establishment of metabolic diseases via the onset of chronic low-grade inflammatory processes. In this instance, Morinaga Milk’s HRB probiotics strain B. breve ​B-3 has been shown to possess attractive beneficial effects in maintaining healthy body weight. Administration of B. breve ​B-3 could improve intestinal barrier function, preventing metabolic inflammation and the development of metabolic syndrome in pre-obese adults. 

Old age: HRB on immunosenescence


At old age, the cellular immune responses are weaker, which, in turn, contributes to the susceptibility to infections and cancer. The elderly are more likely to contract infectious diseases such as respiratory virus infection, which can deteriorate into serious conditions such as pneumonia. Studies have shown that this increased risk correlates with alterations in T cell subpopulation size, cytokine secretion pattern, and antibody production. Consequently, the decline in immune system function can result in impaired vaccine efficacy and increased risk of virus infection. Additionally, levels of bifidobacteria also decline at old age, which may predispose to a reduction in immune response to infections and disease development.

Clinical evidence shows that supplementation of Morinaga Milk’s HRB probiotics strain B. longum ​BB536 could improve waning immunity in the elderly and enhance their resistance to pathogenic viruses. Administration of BB536 to elderly people with influenza vaccination was shown to potentially stimulate neutrophil phagocytic activity and natural killer (NK) cell activity and increase the levels of immunoglobulin A (IgA). As a result, the incidence of influenza virus infections is reduced in the elderly supplemented with B. longum ​BB536. 

With these immunity benefits observed across all age segments, Morinaga Milk’s HRB probiotics serve as useful and worthy probiotics that will help to achieve optimal immune function for lifelong wellbeing. Morinaga Milk continues to explore the full potential of its HRB probiotics in maintaining human health. For more information about Morinaga Bifidobacteria, please visit us at​.


1.        Wong, C. B., Sugahara, H., Odamaki, T. & Xiao, J. Z. Different physiological properties of human-residential and non-human-residential bifidobacteria in human health. Benef. Microbes9​, (2018).

2.        Minami, J., Odamaki, T., Hashikura, N., Abe, F. & Xiao, J. Z. Lysozyme in breast milk is a selection factor for bifidobacterial colonisation in the infant intestine. Benef. Microbes7​, 53–60 (2016).

3.        Odamaki, T. et al.​ Comparative genomics revealed genetic diversity and species/strain-level differences in carbohydrate metabolism of three probiotic bifidobacterial species. Int. J. Genomics2015​, (2015).

4.        Sugahara, H., Odamaki, T., Hashikura, N., Abe, F. & Xiao, J. Differences in folate production by bifidobacteria of different origins. Biosci. microbiota, food Heal.34​, 87–93 (2015).

5.        Sakurai, T., Yamada, A., Hashikura, N., Odamaki, T. & Xiao, J.-Z. Degradation of food-derived opioid peptides by bifidobacteria. Benef. Microbes9​, 675–682 (2018).

6.        Sakurai, T., Odamaki, T. & Xiao, J. Production of Indole-3-Lactic Acid by Bifidobacterium Strains Isolated fromHuman Infants. Microorganisms7​, 340 (2019).

7.        Wong, C. B., Tanaka, A., Kuhara, T. & Xiao, J. Potential Effects of Indole-3-Lactic Acid, a Metabolite of Human Bifidobacteria, on NGF-induced Neurite Outgrowth in PC12 Cells. Microorganisms8​, 398 (2020).

8.        Arboleya, S., Watkins, C., Stanton, C. & Ross, R. P. Gut bifidobacteria populations in human health and aging. Front. Microbiol.7​, 1204 (2016).

9.        Wong, C. B., Iwabuchi, N. & Xiao, J.-Z. Exploring the Science behind Bifidobacterium breve M-16V in Infant Health. Nutrients11​, (2019).

10.       Wong, C. B., Odamaki, T. & Xiao, J.-Z. Beneficial effects of Bifidobacterium longum subsp. longum BB536 on human health: Modulation of gut microbiome as the principal action. J. Funct. Foods