Study: A multi-strain probiotic may support the immune system of older people

This article is part of our October 2022 Immune Health special issue. (link removed).

reference

Sandionigi A, De Giani A, Tursi F, et al. Efficacy of multi-strain probiotic formulation on common infectious disease symptoms and gut microbiota modulation in influenza-vaccinated healthy elderly subjects. Abbassi MS, ed.Biomed Res Int. 2022;2022:3860896.

Study objective

To see whether the probiotic formulation reduced “common infection symptoms” in study participants

Key to take away

Common infection symptoms in older people were less common in those taking a multi-strain probiotic

design

Randomized, double-blind, placebo-controlled, parallel group study

Participant

Fifty healthy elderly subjects aged between 60 and 80 years who had been vaccinated against influenza were randomly assigned to a probiotic group (n=25, of which 17 were women) or a placebo group (n=25, of which 19 were women).

intervention

The study period was 56 days, of which 28 days were with intervention or placebo (3 time points were T0, T28, T56). Participants in the intervention group took 1 unit of a probiotic formulation, and the other group took a placebo containing only the excipients used in the intervention product.

Both groups mixed their learning material with still water and consumed it outside of meals.

The probiotic formulation contained probiotic strains derived from samples of human origin: 1×10⁹Colony forming units (CFU) ofLactiplantibacillus plantarumsubspPlantarum(earlierLactobacillus plantarum) PBS067, 1×10⁹CFU fromBifidobacterium animalissubspLactisBL050, 1×10⁹CFU fromBifidobacterium longumsubspinfantisBI221, 1×10⁹CFU fromBifidobacterium longumsubsplongumBLG240 and excipients commonly used in dietary supplements. The placebo only contained common excipients. The product was supplied by Roelmi HPC (Origgio, Italy).

Evaluated study parameters

• Auftreten von Symptomen einer häufigen Infektionskrankheit (CID). Die CID-Symptome wurden wie folgt beschrieben:
  • Atemwegssymptome (RI; d. h. Erkältung, Husten, Niesen, Halsschmerzen/Juckreiz, verstopfte Nase, mit oder ohne Fieber)
  • Magen-Darm-Symptome (GI; d. h. Erbrechen, Durchfall, Bauchschmerzen)
  • Muskel-Skelett-Symptome (MS; z. B. Spannungskopfschmerzen, Schmerzen, Schwäche, Steifheit, Gelenkgeräusche, eingeschränkte Bewegungsfreiheit)
• Die Forscher berechneten 1 Tag mit begleitenden CID-Symptomen als 1. Sie berechneten die Anzahl der Tage und die Anzahl der Probanden mit mindestens 1 CID.
• Anzahl der Tage mit CID-Symptomen
• Konzentration von Immunglobulin A (IgA) im Speichel
• Gesamte antioxidative Kapazität des Speichels
• Fäkales β-Defensin2 (HBD-2)
• Fäkales Calprotectin
• Vielfalt der Darmmikrobiota

Primary outcome

• Häufiges Auftreten von Symptomen
• Anzahl der Tage mit häufigen Symptomen
• IgA-Konzentration im Speichel
• Gesamte antioxidative Kapazität des Speichels
• Fäkales β-Defensin2 (HBD-2)
• Fäkales Calprotectin
• Vielfalt der Darmmikrobiota

Key findings

Older participants who received multistrain probiotic supplementation were less likely to experience CID symptoms than those in the placebo group (P<0.05). Participants in the probiotic group experienced symptoms on fewer days during the study than participants in the placebo group (P<0.01).

transparency

This study was funded by the Region of Lombardy POR FESR 2014-2020 in support of the development of advances.

Implications and limitations for practice

Research interest in human aging, including the care of older generations with declining immune health, continues to be an important area of ​​clinical research, particularly in the wake of the pandemic. The urgency of how we can better protect our most vulnerable populations, including our elderly, is of global concern. Research with a focus onImmunosenescenceor the way the aging immune system changes throughout life, has become a growing field in the search for ways to support the aging process and potentially improve a person's later years.

One aspect of this research necessarily involves examining the role that the gut microbiome plays in the human immune response. The gut microbiota is known to play an important role in disease response.¹and this role can be compromised in advanced years,²However, what is less understood in the older population is how lifestyle factors such as diet,³Exercise,⁴ and other interventions, including the use of probiotic supplements,⁵can support or strengthen the immune response.

To protect older people from common infectious diseases, vaccination is the standard treatment. In clinical practice, annual vaccinations against influenza and vaccination schedules for other infectious diseases are used to protect this population from serious illness.⁶However, the reality is that vaccines are less effective in older people, a phenomenon highlighted by immunological responses to the Covid-19 vaccines.⁷Healthcare providers have historically used higher-dose vaccines, alternative versions of vaccines, boosters, or vaccines with adjuvants to elicit a robust immune response in aging with limited success.⁸

With this in mind, we are compelled to examine lifestyle factors that may offset some of the common infection symptoms in the elderly. This study focused on examining a population vaccinated against influenza; The aim was then to investigate whether a probiotic mixture could reduce common symptoms of infectious diseases.

Despite the compelling topic, this study has been questioned in some areas. The sample size was relatively small, only 50 people in total. Additionally, the researchers did not assess (or report) baseline symptom scores. It appears that they did not ask study participants whether they had experienced any of the defined common symptoms of an infectious disease (respiratory symptoms such as cold, cough, sneezing, sore airways) on day 0 of the study or in the two weeks before the start of the study. itchy throat, stuffy nose, with or without fever; gastrointestinal symptoms included vomiting, diarrhea, abdominal pain; Musculoskeletal symptoms included tension headaches, pain, weakness, stiffness, joint noise, limited range of motion). Given the small sample size, the researchers might have been able to make a stronger case for the effectiveness of their intervention if they had shown a decrease in symptom scores over time in the intervention group and stability in scores in the placebo group.

In addition, musculoskeletal symptoms accounted for a large proportion of symptoms reported in the placebo group. These symptoms are highly non-specific to infection; For example, in a study on the effectiveness of influenza vaccines, influenza-like illness was defined as "respiratory illness with sore throat, cough, sputum, wheezing or difficulty breathing, accompanied by one or more of the following symptoms: temperature above 37.2 ° C, chills, fatigue, headache or myalgia."⁹In this older cohort, many of these musculoskeletal symptoms are likely due to chronic osteoarthritis and age-related deconditioning and therefore may have been present at baseline. In a small study like this, random assignment of a small number of participants with more severe symptoms at baseline could easily account for the positive results.

The rate at which participants in the placebo group reported symptoms was quite high: 76% reported common symptoms of an infectious disease during the eight weeks of the study. For comparison, the influenza vaccine study cited above found that 23.7% of participants experienced protocol-defined influenza-like illness and 51.4% experienced respiratory illness over approximately 6 months. This further suggests that the symptoms collected were too vague and that the placebo group may have included people who were more likely to report symptoms or who were more symptomatic at baseline.

Research with a focus onImmunosenescenceor the way the aging immune system changes throughout life, has become a growing field in the search for ways to support the aging process and potentially improve a person's later years.

Perhaps the most interesting element, particularly because this study examines common infection symptoms associated with flu and frequent infections, is the curious omission of fever as a common infection symptom. Fever would be one of the first things a doctor would look for in a patient with an acute infection, and its absence as a stand-alone “common symptom of an infectious disease” in this study is puzzling. The authors may have included fever in their symptom checklist, but this is not clear from the article as written, as the exact symptom checklist as seen by participants is not included in the text or supplementary material.

Finally, the use of an objective assessment, such as B. respiratory virus PCR, to confirm that symptoms were due to infection, would have significantly strengthened this study and would likely have been less costly than the reported laboratory parameters.

The authors report no change in salivary IgA concentrations as a result of the study treatment. Fecal beta-defensin 2 increased in the probiotic group compared to baseline, while it did not increase in the placebo group compared to baseline. The more important analysis would have been a direct comparison of these values ​​between the probiotic and placebo groups at baseline and then after the intervention. Based on the included numbers, it appears that fecal beta-defensin-2 levels increased in both groups, but the trend was only statistically significant in the probiotic group; This is a strange result. Not surprisingly, there were changes in the stool microbiome. It would be interesting to see whether changes in the stool microbiome predicted clinical symptoms, but given the size of the study, this analysis may not be conclusive and does not appear to have been performed.

Exploring the connections between the gut microbiome, immunosenescence, vaccinations, and common symptoms associated with infections is an emerging field. This study seems to connect these areas and shows that there may be some effect. However, the initial results will benefit from clarification through future research with larger study sizes and a more rigorous definition of clinical events.

Although this research alone may not convince a doctor to prescribe or recommend probiotic formulations, doctors can still advise their patients to include prebiotics, such as high-fiber vegetables, fruits, and legumes, as well as probiotics, such as fermented or cultured foods, in their diet. This method offers a patient the opportunity to create a microbiota-friendly gut environment and then inoculate that environment with common strains of bacteria naturally found in fermented foods.