Bifidobacterium Infantis 35624: Benefits, Uses & Side Effects

Bifidobacterium infantis 35624 is one of the most clinically studied single-strain probiotics, best known for reducing the core symptoms of irritable bowel syndrome. In a dose-finding trial involving women with IBS, it improved abdominal pain, bloating, bowel dysfunction, and several other symptoms more than placebo by over 20 percent on a global assessment score. But the story of this microbe extends well beyond the gut, touching systemic inflammation, immune regulation, and even a long-standing case of mistaken identity in its very name.

The IBS Evidence

The strongest human data for strain 35624 comes from IBS trials. In a key randomized controlled trial, women with IBS received different doses of the strain or placebo for four weeks. A dose of one hundred million colony-forming units significantly outperformed placebo across multiple symptom measures, including abdominal pain, bloating, incomplete evacuation, straining, and passage of gas. The composite symptom score and the global assessment both showed clinically meaningful improvement.¹ Interestingly, the highest dose tested did not perform as well as the moderate dose, a reminder that “more” does not always mean “better” with probiotics.

A more recent open-label study involving 37 IBS patients found that an eight-week course of the strain was associated with reductions in IBS symptoms, with tolerability rated “very good” or “good” by roughly 89 percent of participants and 83 percent of investigating physicians.² A meta-analysis pooling data from multiple trials concluded that composite probiotics containing this strain could significantly alleviate IBS symptoms without significant adverse effects.³

Worth noting: IBS is a syndrome with a wide range of subtypes and triggers. The best-studied population for this strain has been women with IBS, since several of the landmark trials enrolled predominantly or exclusively female participants. Whether the benefits translate equally to all IBS subtypes and demographics is a fair question the current evidence does not fully answer.

How the Strain Works

The mechanisms behind 35624’s effects are not about simply “adding good bacteria.” This strain acts through at least three distinct pathways that researchers have been teasing apart over the past two decades.

The most distinctive feature is a sugar-based coating on the bacterium’s surface called an exopolysaccharide, or EPS. When researchers engineered a version of the strain that lacked this coating, the stripped bacterium triggered a massive inflammatory response from human immune cells, flooding them with pro-inflammatory signals. The intact strain, with its EPS intact, barely provoked any inflammatory response at all. When the coating was genetically restored, the calming effect returned. In a mouse model of colitis, the coated version prevented disease symptoms while the uncoated mutant failed to protect and actually ramped up inflammatory immune cells in the gut.⁴ So the EPS is not just a passive shield. It actively communicates with the immune system, telling it to stand down.

The second mechanism involves gut barrier integrity. The intestinal lining is held together by tight junction proteins that control what passes between cells. Bioactive factors secreted by 35624 increased the expression of proteins that seal those junctions and decreased one (claudin-2) that loosens them. In a mouse model of colitis, long-term treatment with these secreted factors normalized gut permeability and reduced inflammation.⁵ A “leaky” gut lets molecules through the intestinal wall that trigger immune responses, so tightening these junctions could help explain why the strain reduces both gut and whole-body inflammation.

The third pathway involves direct immune cell modulation. In mice, consuming 35624 shifted immune cell populations in the gut’s lymph tissue, increasing anti-inflammatory immune cells while dampening pro-inflammatory ones. The strain reduced levels of interferon-gamma in immune tissues of both normal mice and those genetically lacking the anti-inflammatory cytokine IL-10.⁶ Separately, feeding the strain to mice increased IL-10-producing immune cells in the gut’s mesenteric lymph nodes through a process that depended on retinoic acid signaling.⁷

Visceral Pain and the Gut-Brain Connection

One of the more striking findings about 35624 is its effect on visceral pain, the deep, diffuse discomfort that drives much of IBS suffering. In an animal model, the strain significantly reduced pain behaviors triggered by pressure distension of the colon in two different rat strains. It raised the pressure threshold at which the first pain behavior appeared and reduced the total number of pain responses. Other probiotic strains tested alongside it did not show the same effect.⁸ This suggests the benefit is not a generic probiotic property but something specific to this strain.

The gut-brain connection goes further. In a maternal separation model of depression in rats, where early-life stress produces depression-like behavior and measurable changes in brain chemistry, treatment with the strain normalized the immune response, reversed behavioral deficits in a standard depression test, and restored levels of noradrenaline in the brainstem.⁹ These are animal studies, and translating them to human mood disorders requires caution. But they point to the strain influencing the nervous system through immune and neurochemical pathways, not just through digestion.

Effects Beyond the Gut

Perhaps the most clinically interesting finding is that 35624 appears to modulate inflammation system-wide, not just in the intestines. A set of human studies examined the strain’s effects in three very different inflammatory conditions: ulcerative colitis, chronic fatigue syndrome, and psoriasis. In all three groups, feeding the strain resulted in reduced plasma C-reactive protein levels compared with placebo. CRP is a broad marker of systemic inflammation measured by a simple blood test, and lowering it across conditions as different as a skin disease and a bowel disease is unusual for any single intervention. Additionally, plasma TNF-alpha was reduced in the chronic fatigue syndrome and psoriasis groups, while IL-6 was reduced in the ulcerative colitis and chronic fatigue syndrome groups.¹⁰

Even in healthy volunteers with no diagnosed inflammatory condition, eight weeks of taking the strain led to significantly reduced pro-inflammatory cytokine secretion by immune cells that were stimulated with bacterial endotoxin in the lab. In other words, the immune cells of healthy people who had been taking the probiotic were less “trigger-happy” when exposed to an inflammatory stimulus.¹⁰ The evidence here is thin enough that nobody should treat 35624 as a replacement for anti-inflammatory medications in serious disease. But the consistency of its immune-dampening effects across multiple conditions and even healthy people suggests the mechanism is robust.

The Allergy Connection

A separate line of research has explored whether the strain’s EPS coating could influence allergic inflammation. In a mouse model of allergic airway disease, intranasal exposure to the purified exopolysaccharide from 35624 significantly decreased eosinophil recruitment to the lungs. Eosinophils are the immune cells heavily involved in asthma and allergic responses. The reduction was accompanied by decreased levels of Th2-associated markers, the branch of the immune system that drives allergic responses. This anti-allergic effect depended on signaling through TLR-2 receptors and the anti-inflammatory cytokine IL-10.¹¹

This is a mouse study using a purified component of the bacterium rather than the live organism, so direct application to human allergies is speculative. But it reinforces the idea that the EPS coating is central to how this strain interacts with the immune system and suggests possible applications in allergic disease that go beyond gut health.

A Metabolite Worth Watching

Beyond its surface coating and secreted proteins, 35624 and closely related bifidobacteria produce a metabolite called indole-3-lactic acid (ILA) as a byproduct of tryptophan metabolism. Research on infant gut microbiomes found that stool samples dominated by B. infantis contained higher amounts of ILA. The bacterium produced significantly more ILA when grown on human milk sugars compared to simple lactose, hinting at how breastfeeding may support this metabolic pathway in early life. In lab experiments, ILA significantly reduced the inflammatory activation triggered by bacterial endotoxin in macrophages and lowered levels of the pro-inflammatory cytokine IL-8 in intestinal cells exposed to inflammatory stimuli.¹²

ILA is part of a broader family of tryptophan-derived metabolites produced by gut bacteria that are increasingly linked to gut barrier health and immune regulation. This is an area where basic science is still catching up, but it may eventually help explain some of the systemic effects observed in clinical studies.

Safety and Side Effects

Across published trials, 35624 has shown a consistently good safety profile. In the eight-week open-label study mentioned earlier, only one participant experienced an adverse event that investigators considered potentially linked to the product: mild nausea, mild abdominal pain, and increased gas during the fourth week. One other participant reported worsened constipation, but this was judged to be within the range of typical IBS symptom fluctuation rather than a product effect.² The meta-analysis of multiple trials found no significant adverse effects associated with the strain.³

That said, the safety data comes almost entirely from otherwise healthy outpatients. The picture may be different for people with compromised immune systems or those who are critically ill and hospitalized. Probiotics in general carry a theoretical risk of causing bloodstream infections in immunocompromised individuals, and no studies have specifically addressed the safety of this strain in such populations.¹³ If you are receiving chemotherapy, are an organ transplant recipient on immunosuppressive drugs, or have another condition that significantly weakens your immune system, talk to your doctor before starting any probiotic, including this one.

For most people, the realistic side effects are mild and transient: temporary gas, bloating, or a brief change in bowel habits during the first week or two. These tend to settle as the gut adjusts.

The Name That Stuck

If you buy a supplement containing this strain, you will almost certainly see it labeled as “Bifidobacterium infantis 35624” or “B. infantis 35624.” The name is technically wrong. Genomic analyses using whole-genome phylogenetics have firmly placed strain 35624 within the subspecies Bifidobacterium longum subsp. longum, not Bifidobacterium longum subsp. infantis. The original classification was based on partial gene sequencing that could not reliably distinguish between the two subspecies, and the error was not corrected until full genome comparisons became routine.¹⁴ A more recent genomic compendium of health-promoting bifidobacteria noted that the strain is still commercially promoted with its incorrect classification.¹⁵

Does this matter for you as a consumer? Not in a practical sense. The strain itself is the same organism regardless of what subspecies label is on the box. All of the clinical and mechanistic data described in this article was generated using the same strain, whether individual papers called it B. infantis 35624 or B. longum subsp. longum 35624. The distinction matters for microbiologists doing taxonomy and for regulatory accuracy, but it does not change what the probiotic does inside your body.

Where it could cause confusion is if you try to compare products. Bifidobacterium longum subsp. infantis is a real subspecies with its own distinct biology, particularly adapted to digesting human milk sugars in infant guts. Strain 35624 does not belong to that subspecies, even though its trade name implies otherwise. If you are specifically looking for a true B. infantis strain for an infant, 35624 is not one, despite the label.

Bifidobacteria in Infants and Children

The naming confusion is especially relevant in pediatrics, where B. infantis (the real subspecies) plays a well-documented role in infant gut colonization and development. True B. infantis strains are uniquely equipped to break down human milk oligosaccharides, the complex sugars in breast milk that human digestive enzymes cannot touch. These strains are among the earliest and most dominant colonizers of a breastfed infant’s gut. A review of the pediatric evidence noted that while B. infantis naturally declines with age and in various diseases, it remains a widely used probiotic with documented benefits for infant and child health.¹⁶

Strain 35624, however, has been studied primarily in adults. Its clinical trials enrolled adult IBS patients, adult volunteers, and adults with inflammatory conditions. When researchers discuss B. infantis in the context of infant nutrition and gut colonization, they are generally referring to genetically distinct strains from the true infantis subspecies, not to 35624. Parents shopping for a probiotic for their infant should be aware of this distinction, since product marketing does not always make it clear.

How to Take It and What to Expect

Strain 35624 is commercially available under the brand name Alflorex (sold as Align in some markets). The dose used in the best clinical trial was one hundred million colony-forming units taken once daily. This is a lower dose than many probiotic supplements on the market, which often advertise billions of CFUs as a selling point. The dose-finding trial actually found that higher doses were less effective than this moderate one, though the reasons for that are not fully understood.¹

In the clinical trials, benefits for IBS symptoms emerged within the four-week study period. The eight-week open-label study provided symptom data across its full duration. If you are trying the strain for IBS, giving it at least four weeks before judging whether it helps is reasonable based on the trial timelines. Probiotics in general do not colonize the gut permanently in adults; they transit through and exert their effects while you keep taking them, so stopping typically means the benefits fade.

No special dietary changes are required to take the strain, and it does not need to be taken with food, though following the specific product’s label instructions is sensible. Unlike some probiotics that require refrigeration, the commercial formulations of 35624 are typically shelf-stable, though storage conditions can vary by product format.

Why One Strain Is Not Interchangeable With Another

A persistent misconception about probiotics is that they are roughly interchangeable, as though any Bifidobacterium product will deliver similar benefits. The research on 35624 argues against this. Its EPS coating, the specific structure that drives much of its immune-modulating activity, is genetically encoded and particular to this strain. When that coating was removed in the lab, the bacterium not only lost its anti-inflammatory effects but actively provoked inflammation.⁴ Similarly, in the visceral pain study, other probiotic strains tested alongside 35624 did not reduce pain behaviors.⁸

This strain specificity is one of the strongest lessons from the 35624 literature. The clinical evidence applies to this particular strain at the studied dose, not to bifidobacteria in general, not to other strains with similar-sounding names, and not to multi-strain blends that happen to include a Bifidobacterium component. When choosing a probiotic for a specific purpose, the strain number matters at least as much as the species name on the label.