Whey peptide-based enteral diet attenuated elastase-induced emphysema with increase in short chain fatty acids in mice

Abstract

Background: Systemic inflammation is present in chronic obstructive pulmonary disease (COPD). A whey peptide-based enteral diet reduce inflammation in patients with COPD, but its effect on COPD development has not been determined. On the other hand, it is known that short chain fatty acids (SCFAs), which are produced by micro-flora in the gut, attenuates bronchial asthma in mice model.

Methods: Mice with elastase-induced emphysema were fed with 1 of 3 diets (control diet, whey peptide-based enteral diet, or standard enteral diet) to determine the effects of whey peptide-based enteral diet on emphysema and on cecal SCFAs.

Results: The whey peptide-based enteral diet group exhibited fewer emphysematous changes; significantly lower total cell counts in bronchoalveolar lavage fluid (BALF); and significantly higher cecal SCFA levels than either the control or standard enteral diet groups. The total cell count was inversely correlated with total cecal SCFA levels in these three diet groups.

Conclusions: The whey peptide-based enteral diet attenuates elastase-induced emphysema through the suppression of inflammation in the lung. This may be related to the increase in cecal SCFA.

Figures

Fig. 1

Changes in body weight in the 4 weeks following elastase instillation to induce emphysema. Results are expressed as mean ± standard error of mean. Symbols:, phosphate buffered saline-instilled mice with control diet (sham; n = 4);, elastase-instilled mice on the control diet (n = 4);,elastase-instilled mice on the whey peptide-based enteral diet (n = 4);, elastase-instilled mice on the standard enteral diet (n = 4). There were no significant differences at any weeks before and after elastase instillation between the 4 groups, compared using Mann–Whitney U tests

Fig. 2

Whey peptide suppressed elastase-induced emphysematous changes. Histologically in the control diet groups, elastase-instillation induced emphysematous lesions with enlargement and disruption of alveolar walls (a and b). These changes were remarkably suppressed by whey peptide (c), while these were not suppressed by standard enteral diet (d). Changes in mean linear intercept (MLI), one of the morphologic parameters, were shown at e. In the control diet groups these were enlarged by elastase-instillation. The enlargements were suppressed by the whey peptide, while those were not suppressed by the standard enteral diet. Results are expressed as mean ± standard deviation of mean and compared using Mann–Whitney U tests. The sham group consisted of phosphate buffered saline-instilled mice on a control diet

Fig. 3

Whey peptide suppressed the increase in total cell counts of BALF. In the control diet groups elastase instillation increased total cell and macrophage counts in the BALF. The increases were significantly suppressed by whey peptide, while these were not suppressed by standard enteral diet (a and b). In the control diet groups elastase instillation increased lymphocyte and neutrophil counts. The significant increases were similarly observed in the standard enteral diet group, while the increases were not proved in the whey peptide diet group (c and d). Results are expressed as mean ± standard deviation of mean and compared using Mann–Whitney U tests. The sham group consisted of phosphate buffered saline-instilled mice on a control diet

Fig. 4

Whey peptide increased short fatty chain acid levels. In elastase-instilled mice whey peptide increased total levels of SCFA (a), acetic acid (b), propionic acid (c) and butyric acid (d) while the increases were not proved by standard enteral diet. Results are expressed as mean ± standard deviation of mean and compared using Mann–Whitney U tests. The sham group consisted of phosphate buffered saline-instilled mice on a control diet

Fig. 5

Total cell count in the BALF was inversely correlated with total cecal SCFA levels. Total cell count in the BALF from elastase-instilled mice was inversely correlated with total cecal SCFA levels