How Beneficial is the Use of Probiotic Supplements for the Aging Gut?

Siobhán Cusack; Marcus J Claesson; Paul W O'Toole

Disclosures

Aging Health. 2011;7(2):179-186. 

In This Article

Probiotics in Older Populations

From all of the aforementioned findings, there would appear to be a very good case for the administration of probiotics to the elderly population. To summarize, these individuals have a range of physiological, immunological and microbiological alterations, relative to younger subjects, that indicate that introduction of beneficial microorganisms would directly or indirectly improve health.

Probiotics: Choice of Strains, Strategies & Appropriate Subjects

Several recent comprehensive reviews have summarized the major benefits associated with probiotic consumption in older adults,[18,30] which largely overlap with those expected or desired in younger adults. Such benefits include increased levels of bifidobacteria,[15] a reduction in the degree of constipation,[31] enhanced innate immunity[32] and reduced inflammation.[33] However, presumably not all negative studies, meaning those showing no change or no benefit in the health of the consumers, are eventually published, and furthermore not all published studies report positive outcomes. For example, recent administration of a probiotic yoghurt and a probiotic compound (galacto-oligosaccharide) had no great effect on the major groups of the microbiota in older adults; consumption did not significantly affect diversity or temporal stability of these groups, as measured by molecular methodology.[34] Although the yoghurt contained Bifidobacterium lactis Bb-12 (and Lactobacillus acidophilus LaCH-5), no general increase of bifidobacteria was recorded. When evaluating outcomes of trials with probiotics, a noteworthy qualifier is that achieving beneficial effects is usually dependent upon the genus and species of the probiotic organism and in many cases is also strain dependent. Lactobacillus delbrueckii subspecies bulgaricus (L. bulgaricus) OLL1073R-1 is a strain previously shown to have immunomodulatory properties in mouse models.[35] Administration of yoghurt fermented by this strain to older people (n = 142; a median age of 74.5 years) significantly reduced the incidence and severity of winter colds and general upper respiratory symptoms. This improvement was accompanied by an increase in natural killer cell activity in the subjects receiving the yoghurt.[35] Preclinical validation of beneficial effects in in vitro systems or animal models may thus be beneficial for strain selection, but obviously cannot replace human trials.

The vast majority of commercially available probiotics are species of Lactobacillus or Bifidobacterium that were selected before the advent of culture-independent microbiota analysis. Major selection criteria, pragmatically enough, were the possession by strains of demonstrable 'probiotic-related' traits, which were typically acid and bile resistance (arguably survival traits, not true host-interaction phenotypes), the ability to adhere to cultured cells and, critically, technological stability of the strain in the processed consumer product.[36] As the market-share of functional foods increased, as competition increased and as discerning consumers became more brand-aware, additional characterization of probiotic strains included reduction in infection risks, modification of dietary components and stimulation of the innate or adaptive immune response. However, now that we have a better understanding of the human intestinal microbiota, a new paradigm for selecting probiotic species and strains presents itself, which is particularly compelling for older populations with the distinctive dynamic microbiota composition discussed earlier. For example, older people are susceptible to 'inflammaging',[37] a progressive increase in the proinflammatory markers, as well as immunosenescence exemplified by loss of naive CD4+ T cells.[38] It has been suggested that this persistent and increasing inflammation in older people is associated with changes in the microbiota,[39] including reductions in mucus-adherent bifidobacteria.[40] However, in addition to conventional probiotic administration, persistent inflammation could arguably be targeted by administration of newly recognized anti-inflammatory bacteria such as F. prausnitzii, which, as noted previously, has been shown to be depleted in inflammatory bowel disease patients[41] and to be anti-inflammatory in humans with inflammatory bowel disease and in murine colitis models.[20] Our recent analyses of the microbiota of older adults in Ireland confirmed that the prevalence of the genus Faecalibacterium varied significantly between individuals,[28] supporting the notion that levels of this organisms might be suitable for therapeutic intervention in older people with intestinal inflammation. Such intervention could take the format of direct administration of F. prausnitzii (technically challenging for an obligate anaerobe not easily grown in laboratory culture), administration of prebiotics (although specificity for stimulating growth of only F. prausnitzii may be hard to achieve), or by administering probiotics that target competing elements in the microbiota (an attractive notion, still in the conceptual phase only).

Given the relationships between the microbiota and diet utilization, energy extraction and conversion to more readily metabolizable compounds, another probiotic strategy might be to rationally modify the microbiota to enhance nutritional efficiency. Our recent culture-independent analysis of the microbiota of several hundred subjects identified major interindividual changes in the proportions of phyla, genera and Clostridium clusters associated with SCFA production.[28] Modulation of the microbiota in individuals in whom proportions of butyrate-producing bacteria are low has the potential to not only improve energy extraction from the diet, but also to improve bone structure owing to indirect but significant effects upon mineral absorption and deposition.[42] Clearly this would be of major benefit to older individuals for whom bone health is a major issue. While the desired increase in microbiota proportions of SCFA-producing bacteria could theoretically be accomplished by consuming prebiotics, there are significant problems in achieving specificity of bacterial growth promotion.[43] Thus an alternative probiotic strategy might be direct administration of a culture or cultures of organisms known to produce SCFA, preferably in association with defined dietary supplementation. Clearly such organisms should be well defined (i.e., genome sequenced) and devoid of undesirable properties, such as antibiotic resistance genes.

A pertinent issue is the range of beneficial responses that may reasonably be expected upon administration of probiotic cultures or products to a cohort of older subjects, as with any age group. Kleerebezem and colleagues have coined the provocative phrase a 'bandwidth of human health' and the accompanying concept that the measurable efficacy of a probiotic will logically depend on where in this bandwidth the health status of a particular consumer is initially located, for example pretreatment [Kleerebezem M, Pers. Comm.]. There is both clinical and molecular evidence to support this idea. For example, in consumption trials among older adults over a 9-week period, Gill and colleagues reported that the greatest increases in biomarkers of enhanced immune function were measured in subjects with the poorest pretreatment levels.[32] In human subjects consuming probiotic lactobacilli, variation between people was the largest source of variation in the transcriptome of the epithelium of the small intestine.[44,45] Thus, the magnitude of response or measurable physiological benefit of the individual consumer of a probiotic product may vary significantly. This realization has not been consistently applied to the testing of probiotics for the older adult (or most other groups), making uniform interpretation of their health benefits more challenging.[46] Older adults as a group in society will typically span a greater range in health-status (from healthy and independent living to frail and dependent on assistance). They are known to have a microbiota in flux that varies significantly more between individuals than in a younger adult cohort;[28] these factors should be borne in mind when designing clinical trials.

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